Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Atezolizumab · 82 trials · 73 indications
IDFS event is defined as the time from randomization to the first occurrence of the following events: ipsilateral invasive breast tumor recurrence, ipsilateral local-regional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, death from any cause.
TACE PFS is defined as the time from randomization to untreatable progression or TACE failure/refractoriness or any cause of death, whichever occurs first, as determined by the investigator (INV).
PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause (whichever occurred first), as determined by an IRF according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm) or unequivocal progression of existing non-target lesions. Kaplan-Meier (KM) method was used to estimate median PFS.
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Severity of AEs was graded using NCI CTCAE v5.0. Grade 3=Severe/medically significant but not immediately life-threatening, hospitalization/prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living; Grade 4=Life-threatening consequences, urgent intervention indicated; Grade 5=Death related to AE.
PFS was defined as the time from randomization to the first occurrence of PD, as determined by an IRF according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm) or unequivocal progression of existing non-target lesions. Kaplan-Meier (K-M) method was used to estimate median PFS.
PFS was defined as the time from randomization to the first occurrence of PD, as determined by an IRF according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate median PFS.
PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
RFS is defined as the time from randomization to the first documented occurrence of intrahepatic or extrahepatic HCC as determined by an IRF, or death from any cause (whichever occurs first).
AE=untoward medical occurrence in participant administered a pharmaceutical product, regardless of causal attribution. AE=any unfavorable \& unintended sign, symptom/disease temporally associated with the use of pharmaceutical product, whether/not considered related to it. Severity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0). Grade 1=Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3=Severe/medically significant, but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to AE. Percentages have been rounded off.
AE=any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. AE=any unfavorable and unintended sign, symptom/disease temporally associated with the use of a pharmaceutical product, whether/not considered related to it. Severity was graded according to NCI CTCAE v5.0. Grade 1=Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living (ADL); Grade 3=Severe/medically significant, but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated; disabling; or limiting self-care ADL; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to AE. imAEs are events that resemble autoimmune diseases and are known side effects of immune checkpoint inhibitors.
PFS was defined as the time from randomization to the first occurrence of disease progression as determined locally by RECIST or death from any cause during treatment, whichever occurs first.
The incidence of serious adverse events (SAEs) related to atezolizumab.
pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST) (i.e., ypT0/is ypN0 in the current American Joint Committee on Cancer \[AJCC\] staging system, 8th edition). Treatment comparison was made using Cochran-Mantel-Haenszel test stratified by disease stage (T2 vs. T3-4) and hormone receptor status (estrogen receptor (ER) positive and/or progesterone receptor (PgR) positive vs. ER negative and PgR negative).
pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST) (i.e., ypT0/is ypN0 in the current American Joint Committee on Cancer \[AJCC\] staging system, 8th edition). Treatment comparison was made using Cochran-Mantel-Haenszel test stratified by disease stage (T2 vs. T3-4) and hormone receptor status (ER positive and/or PgR positive vs. ER negative and PgR negative).
Time from the date of randomization to the date of first documentation of disease progression or death due to any cause, whichever occurs first based on investigator assessment using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)
Time from the date of randomization to the date of death due to any cause
OS was defined as the time from randomization to death from any cause.
PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
OS was defined as the time from randomization to death from any cause.
PFS was defined as the time from randomization to the first occurrence of progressive disease (PD) or death from any cause whichever occurs first as determined by an IRF according to RECIST v1.1. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/= 5 millimeters (mm).
OS was defined as time from randomization to death from any cause. Participants without a reported death event at the time of the analysis were censored on the date they were last known to be alive. If no post-baseline data were available, OS was censored at the date of randomization +1 day.
OS was defined as time from randomization to death from any cause. Participants without a reported death event at the time of the analysis were censored on the date they were last known to be alive. If no post-baseline data were available, OS was censored at the date of randomization +1 day.
Investigator-assessed PFS is defined as the time from randomization to the occurrence of disease progression, as determined by the investigator from tumor assessments per RECIST v1.1, or death from any cause during the study, whichever occurs first.
Investigator-assessed PFS is defined as the time from randomization to the occurrence of disease progression, as determined by the investigator from tumor assessments per RECIST v1.1, or death from any cause during the study, whichever occurs first.
Overall Survival (OS) is defined as the time from randomization to death from any cause.
Overall Survival (OS) is defined as the time from randomization to death from any cause.
PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 millimeters (mm).
PFS is defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1, or death from any cause, whichever occurs first.
OS is defined as the time from randomization to death due to any cause.
OS is defined as the time from randomization to death due to any cause.
PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurred first.
DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm.
DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. DFS was analyzed in participants with disease stage II-IIIA. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm.
DFS was defined as the time from randomization to the first recurrence of NSCLC or occurrence of new primary NSCLC as determined by the investigator or death, whichever occurs first. DFS was analyzed in PD-L1 ≥1% subpopulation within the Stage II-IIIA population. Kaplan-Meier methodology was used to estimate the median DFS for each treatment arm.
Percentage of participants who died among TC1/2/3 or IC1/2/3 subgroup of PP-ITT were reported. TC1 = presence of discernible programmed death-ligand 1 (PD-L1) staining of any intensity in \>/=1% and \<5% TCs; TC2: presence of discernible PD-L1 staining of any intensity in \>/=5% and \<50% TCs; TC3 = presence of discernible PD-L1 staining of any intensity in \>/=50% TCs; IC1 = presence of discernible PD-L1 staining of any intensity in ICs covering between \>/=1% and \<5% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma; IC2 = presence of discernible PD-L1 staining of any intensity in ICs covering between \>/=5% and \<10% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma; IC3 = presence of discernible PD-L1 staining of any intensity in ICs covering \>/=10% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma.
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology.
Participants preference was assessed based on the Question 1 of PPQ. Question 1 (All things considered, which route of administration did you prefer?) asks participants to report their preference for the route of administration (IV, SC, or no preference). A point estimate with associated 95% CI for the percentage of participants who preferred atezolizumab SC was calculated. Participants experiencing any of the following events: treatment withdrawal prior to eligibility for PPQ, or death without answering Question 1 of PPQ, or treatment not started; were excluded from the analysis set. Participants who answered Question 1 of the PPQ without having at least 2 consecutive administrations of treatment with each administration modality (SC and IV) were excluded from the analysis. Percentages have been rounded off. As planned, participant preference was summarized and presented by overall (all participants) and by randomized treatment sequence using FAS.
DFS-rate
pCR is defined as no evidence of vital residual tumor cells on hematoxylin and eosin evaluation of the complete resected gastric/GEJ specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST), which will be reviewed by local pathologist..
A confirmed objective response rate (ORR) was defined as the percentage of participants with a confirmed objective response (OR), characterized by a complete response (CR) or a partial response (PR), on 2 consecutive occasions ≥ 4 weeks apart, as determined by the investigator per RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions \& normalization of tumor marker level. Additionally, any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.
PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1 or death from any cause (whichever occurs first)
Objective response rate (ORR), defined as the proportion of participants with a complete response (CR) or partial response (PR) on two consecutive occasions \>= 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
Objective response rate (ORR) was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions \>=4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
The primary endpoint for this study is overall response rate in PDL1 negative melanoma to combination anti-PD-L1 therapy and anti-VEGF therapy by RECIST criteria. The proportion of patients with complete response or partial response as best response to therapy will be summarized and presented with a two-sided, 90% Wald confidence interval.
The proportion of participants in each tumour-defined cohort who have a complete response (CR) or partial response (PR) to treatment, as defined by RECIST 1.1.
ORR was defined as the percentage of participants with a complete response (CR) defined as disappearance of all target lesions, or partial response (PR) defined as at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR, on two consecutive occasions \>= 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline) or unequivocal progression of existing non-target lesions. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of ≥5 mm. Kaplan-Meier (KM) methodology was used to estimate the median PFS.
PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions.
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Investigator-assessed objective response rate was defined as the proportion of participants who had a confirmed best overall response of either PR or CR per RECIST v1.1.
Investigator-assessed PFS by RECIST v1.1 was defined as the time from the first dose of study drug to the time of PD or death from any cause during the study, whichever occurred first.
Tumor response was assessed by the IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% confidence interval (CI) was calculated using the Clopper-Pearson method.
Tumor response was assessed by the IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% confidence interval (CI) was calculated using the Clopper-Pearson method.
Tumor response was assessed by the investigator according to modified RECIST. CR was defined as disappearance of all target and non-target lesions and no new measurable or unmeasurable lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a confirmed objective response of CR or PR was reported. The exact 95% CI was calculated using the Clopper-Pearson method.
ORR was the percentage of participants whose confirmed best overall response was either a Partial Response (PR) or a Complete Response (CR) based upon the IRF assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm); PR:greater than (\>) or equal to (=) 30 percent (%) decrease from baseline in sum of diameters of target lesions, non-progressive disease (PD) non-target lesions and no new lesions. Results were reported by line of therapy and programmed death-ligand 1 (PD-L1) Expression Subgroup (tumor cell \[TC\]3 \[TC3\] or tumor-infiltrating immune cell \[IC\] 3 \[IC3\], TC3 or IC2/3, TC2/3 or IC2/3).
MPR rate is defined as the proportion of participants with =\<10% residual viable tumor in the tumor bed at the time of surgery, as assessed by central pathological review.
pCR was defined as the absence of any viable primary tumor at time of surgical resection, as determined by local pathologic review. The pCR rate was defined as the percentage of participants who achieved a pCR. pCR rate was calculated for each arm, along with the 95% confidence interval (CI) estimated using the Clopper-Pearson method and the 95% CI for difference in rates was estimated using the Wald method with continuity correction. Participants with missing or no pathologic response assessment were classified as non-responders. Percentages have been rounded off to the nearest whole number.
ORR is defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
DCR is defined as the percentage of participants with CR, PR, or stable disease (SD) at 16 weeks. Per RECIST v1.1, CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.
The first patient in each cohort and regimen will be observed for safety for one week after the administration of RO6874281and atezolizumab +-bevacizumab, prior to enrollment of additional patients in a cohort. The DLT will be counted for each dose separately and each patient will contribute one single representative data point.
The MTD is defined as the highest dose with less than 33% probability of dose limiting toxicity (DLT).
The recommended dose is defined as the lowest safe dose with the best likelihood for clinical benefit.
Objective response rate (ORR) defined as the number of patients who achieved an objective response (partial response (PR) plus complete response (CR)) confirmed 28 or more days later, as determined by the Investigator using RECIST v1.1 and modified RECIST criteria at any time during the study divided by the number of response-evaluable patients.
Tumor response assessment was performed by the investigator according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake \</=mediastinum), or 3 (uptake \<mediastinum but \</=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow; and normal/IHC-negative bone marrow morphology. 90% confidence interval (CI) for percentage of responders was calculated using Clopper-Pearson method. All PET evaluable 1L FL and 1L DLBCL patients with at least one dose of atezolizumab were included in efficacy population.
Phase (Ph) 1a: Pre-dose on Day 1, Cycles 1-4, 8, 16, every eight cycles (Q8C), at discontinuation (DC), every 30 days up to 120 days (cycle length 21 days); Phase 1b without Chemotherapy: Pre-dose on Day 1, Cycles 1-4, 8, then Q8C, DC (cycle length 21 days); Phase 1b (Chemotherapy Cohorts and Q4W): Pre-dose on Day 1, Cycles 1-4, 8, 12 and 16, then DC (cycle length 21/28 days).
Phase 1b (without Chemotherapy): Pre-dose on Day 1, Cycles 1-4, 8, then Q8C, at DC, every 30 days up to 120 days (cycle length 21 days); Phase 1b (Chemotherapy Cohorts and Q4W): Pre-dose on Day 1, Cycles 1-4, 8, 12 and 16, then DC (cycle length 21/28 days).
Complete response (CR) was evaluated through use of PET-CT scans, using the Modified Lugano 2014 criteria. Response was determined by the IRC.
Primary end point was positron emission tomography (PET) CR at EOI by IRC according to modified Lugano classification using PET/CT scan. CR was defined as a score of 1 (no uptake above background), 2 (uptake less than or equal to \[\</=\] mediastinum), or 3 (uptake less than \[\<\] mediastinum but \</=liver) with or without a residual mass on PET 5-point scale (5-PS), for lymph nodes and extralymphatic sites; no new lesions; no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow; and normal/immunohistochemistry (IHC)-negative bone marrow morphology. All PET evaluable 1L FL and 1L DLBCL participants with at least one dose of atezolizumab were included in efficacy population.
Seroconversion is defined as the presence of at least one of the following autoantibodies: anti-nuclear antibody, antidouble-stranded deoxyribose nucleic acid (DNA), cytoplasmic anti-neutrophil cytoplasmic antibody, and perinuclear anti-neutrophil cytoplasmic antibody.
| Arm | Type | Description |
|---|---|---|
| Atezolizumab + Bevacizumab + Tiragolumab | EXPERIMENTAL | Atezolizumab plus bevacizumab plus tiragolumab will be administered every 3 weeks (Q3W) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. |
| Atezolizumab + Bevacizumab + Placebo | PLACEBO_COMPARATOR | Atezolizumab, bevacizumab plus placebo will be administered Q3W until unacceptable toxicity or loss of clinical benefit as determined by the investigator. |
| Atezolizumab | EXPERIMENTAL | Participants will receive IV infusion of atezolizumab on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by investigators. |
| Atezolizumab Monotherapy | EXPERIMENTAL | Participants will continue to receive atezolizumab monotherapy as per parent protocol, until disease progression or beyond if the participant continues to derive clinical benefit as judged by the investigator and if allowed by the parent study or local prescribing information until death; withdrawal of study consent; unacceptable toxicity; pregnancy; participant non-compliance; or study termination by the Sponsor, whichever occurs first. |
| Combined Agents with Atezolizumab | EXPERIMENTAL | Participants will continue to receive atezolizumab with other agent(s) as per parent protocol, until disease progression or beyond if the participant continues to derive clinical benefit as judged by the investigator and if allowed by the parent study or local prescribing information until death; withdrawal of study consent; unacceptable toxicity; pregnancy; participant non-compliance; or study termination by the Sponsor, whichever occurs first. |
| Comparator Treatment | ACTIVE_COMPARATOR | Participants will continue to receive comparator agent(s) as per parent protocol, until disease progression or beyond if the participant continues to derive clinical benefit as judged by the investigator and if allowed by the parent study or local prescribing information until death; withdrawal of study consent; unacceptable toxicity; pregnancy; participant non-compliance; or study termination by the Sponsor, whichever occurs first. |
| Arm A: Placebo + Trastuzumab Emtansine | ACTIVE_COMPARATOR | Participants will receive an intravenous (IV) infusion of placebo prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles. |
| Arm B: Atezolizumab + Trastuzumab Emtansine | EXPERIMENTAL | Participants will receive an IV infusion of atezolizumab prior to the IV infusion of trastuzumab emtansine on Day 1 of each 21-day cycle for a total of 14 cycles. |
| Atezolizumab + Lenvatinib or Sorafenib | EXPERIMENTAL | Participants will receive atezolizumab plus lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator. |
| Lenvatinib or Sorafenib | ACTIVE_COMPARATOR | Participants will receive lenvatinib or sorafenib. Treatment will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator. |
| Arm A: atezolizumab + bevacizumab + TACE | EXPERIMENTAL | Participants will receive atezolizumab plus bevacizumab on Day 1 of a 21-Day cycle, after every on-demand transarterial chemoembolization procedure. |
| Arm B: TACE alone | ACTIVE_COMPARATOR | Participants will receive on-demand transarterial chemoembolization. |
| Atezolizumab + Tiragolumab + PC | EXPERIMENTAL | Participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase. |
| Placebo + PC | PLACEBO_COMPARATOR | Participants will receive atezolizumab matching placebo and tiragolumab matching placebo on Day 1 of each 21-day cycle during the study followed by paclitaxel and cisplatin on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity, during the induction treatment phase. |
| Atezolizumab + Bevacizumab | EXPERIMENTAL | Participants will receive atezolizumab 1200 mg intravenous (IV) infusions Q3W (dosed in 3-week cycles) + bevacizumab 15 mg/kg IV Q3W (dosed in 3-week cycles) |
| Atezolizumab + Tiragolumab | EXPERIMENTAL | Participants will receive atezolizumab administered intravenously (IV) on Day 1 of each 28-day cycle followed by tiragolumab administered IV on Day 1 of each 28-day cycle for a maximum of 13 cycles. |
| Durvalumab | ACTIVE_COMPARATOR | Participants will receive durvalumab administered IV during each 28-day cycle for a maximum of 13 cycles. |
| Treatment A | EXPERIMENTAL | Participants will receive atezolizumab, bevacizumab, paclitaxel or pemetrexed, and carboplatin (in this order) by intravenous (IV) injection on Day 1 of each 21-day cycle for 4 cycles in the induction treatment. In the maintenance phase, participants will be treated with atezolizumab, bevacizumab and pemetrexed (if given in the induction phase) until unacceptable toxicity or loss of clinical benefit. |
| Treatment B | PLACEBO_COMPARATOR | Participants will receive placebo, bevacizumab, paclitaxel or pemetrexed, and carboplatin (in this order) by intravenous (IV) injection on Day 1 of each 21-day cycle for 4 cycles in the induction treatment. In the maintenance phase, participants will be treated with placebo, bevacizumab and pemetrexed (if given in the induction phase) until unacceptable toxicity or loss of clinical benefit. |
| Tiragolumab + Atezolizumab | EXPERIMENTAL | Participants will receive atezolizumab followed by tiragolumab every 3 weeks (Q3W) on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity. |
| Placebo + Atezolizumab | PLACEBO_COMPARATOR | Participants will receive atezolizumab followed by placebo Q3W on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity. |
| Arm A (atezolizumab plus bevacizumab) | EXPERIMENTAL | Participants will receive Atezolizumab + Bevacizumab until disease recurrence or unacceptable toxicity. |
| Arm B (active surveillance) | NO_INTERVENTION | Active surveillance of participants. |
| Atezolizumab plus Nab-Paclitaxel | EXPERIMENTAL | Participants will receive Atezolizumab via intravenous (IV) infusion on Days 1 and 15 of every 28-day cycle in combination with Nab-Paclitaxel on Days 1, 8, and 15 (individually selected by the investigator) until disease progression, or unacceptable toxicity, additionally until loss of clinical benefit as determined by the investigator or participant decision to discontinue treatment. |
| Cohort 1 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | EXPERIMENTAL | TNBC participants with programmed death-ligand 1 (PD-L1) non-positive received a combination of paclitaxel, 80 milligrams per meter square (mg/m\^2), intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, orally (PO), once daily (QD), from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first. |
| Cohort 1 Arm B: Ipatasertib + Placebo + Paclitaxel | EXPERIMENTAL | TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m\^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first. |
| Cohort 1 Arm C: Placebo + Placebo + Paclitaxel | EXPERIMENTAL | TNBC participants with PD-L1 non-positive received a combination of paclitaxel, 80 mg/m\^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab-matching placebo, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first. |
| Cohort 2 Arm A: Ipatasertib + Atezolizumab + Paclitaxel | EXPERIMENTAL | TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m\^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib, 400 mg, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first. |
| Cohort 2 Arm B: Placebo+ Atezolizumab + Paclitaxel | EXPERIMENTAL | TNBC participants with PD-L1 positive received a combination of paclitaxel, 80 mg/m\^2, IV infusion on Days 1, 8, and 15 of each 28-day cycle and ipatasertib-matching placebo, PO, QD, from Day 1 to Day 21 of each 28-day cycle and atezolizumab, 840 mg, IV infusion on Day 1 and 15 of each 28-day cycle until loss of clinical benefit, unacceptable toxicity, or withdrawal of consent, whichever occurred first. |
| Atezolizumab + Carboplatin + Etoposide | EXPERIMENTAL | Participants will receive intravenous infusions of atezolizumab 1200 milligrams (mg) in combination with carboplatin to achieve an initial target area under the concentration-time curve (AUC) of 5 milligrams per milliliter per minute (mg/mL/min), followed by intravenous infusion of etoposide 100 milligrams per square meter (mg/m\^2) on days 1 through 3 of each cycle during the induction phase (21-day cycle for four/six cycles). On Days 2 and 3, participants will receive etoposide alone. After the induction phase, participants will begin maintenance therapy with atezolizumab every 3 weeks until PD, unacceptable toxicity, loss of clinical benefit or study termination by the Sponsor. |
| Bevacizumab plus chemotherapy | ACTIVE_COMPARATOR | Bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m\^2 intravenously on day 1 every 3 weeks |
| Atezolizumab plus bevacizumab plus chemotherapy | EXPERIMENTAL | Atezolizumab 1200mg intravenously on day 1 every 3 weeks plus bevacizumab 15mg/kg intravenously on day 1 every 3 weeks plus 4-6 cycles of carboplatin AUC 5 plus pemetrexed 500mg/m\^2 intravenously on day 1 every 3 weeks |
| Atezolizumab +ddAC-PacHP | EXPERIMENTAL | Participants will receive atezolizumab (atezo) 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 \& cyclophosphamide 600 mg/m2 IV), followed by atezo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with initial 8mg/kg IV loading dose) Q3W for 4 cycles, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant and adjuvant setting: atezo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo must be discontinued. |
| Placebo + ddAC-PacHP | PLACEBO_COMPARATOR | Participants will receive placebo 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 \& cyclophosphamide 600 mg/m2 IV), followed by placebo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W for 4 cycles \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant \& adjuvant setting: placebo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo must be discontinued. |
| Atezolizumab (Part 2) | EXPERIMENTAL | Atezolizumab |
| Cohort 1: Atezolizumab+rHuPH20 (Part 1) | EXPERIMENTAL | Atezolizumab+recombinant human hyaluronidase (rHuPH20), followed by Atezolizumab |
| Cohort 2: Atezolizumab+rHuPH20 (Part 1) | EXPERIMENTAL | Atezolizumab+rHuPH20, followed by Atezolizumab |
| Cohort 3: Atezolizumab+rHuPH20(Part 1) | EXPERIMENTAL | Atezolizumab+rHuPH20, followed by Atezolizumab |
| Atezolizumab + rHuPH20 (Part 2) | EXPERIMENTAL | Atezolizumab + rHuPH20 |
| Arm A | ACTIVE_COMPARATOR | Cisplatin 50mg/m2 or carboplatin AUC 5 + paclitaxel 175mg/m2+ bevacizumab 15mg/kg i.v D1 Q3W. Patients who achieve a complete response after ≥6 treatment cycles may be allowed to continue only on biologic therapy, namely bevacizumab, upon investigator discussion. |
| Arm B | EXPERIMENTAL | cisplatin 50mg/m2 or carboplatin AUC 5 + paclitaxel 175mg/m2 + bevacizumab 15mg/kg + atezolizumab 1200mg i.v, D1 Q3W.Patients who achieve a complete response after ≥6 treatment cycles may be allowed to continue only on biologics therapy, namely bevacizumab plus atezolizumab, upon investigator discussion. |
| Sorafenib | ACTIVE_COMPARATOR | Participants will receive Sorafenib until unacceptable toxicity or loss of clinical benefit as determined by the investigator |
| Placebo | PLACEBO_COMPARATOR | Participants will receive Placebo on day 1 of each 3-week treatment cycle |
| Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab | EXPERIMENTAL | Participants in the primary tumor-reductive surgery group will receive paclitaxel, carboplatin, atezolizumab intravenous (IV) infusion on Day 1 of each 21-day cycle for a total of 6 cycles, and bevacizumab IV infusion starting with Cycle 2 for a total of 5 cycles, followed by maintenance therapy bevacizumab with atezolizumab for a total of 22 cycles of atezolizumab and 21 cycles of bevacizumab. Participants in the neoadjuvant therapy group will receive paclitaxel, carboplatin and atezolizumab for 6 cycles and bevacizumab for 4 cycles. Interval surgery will occur between cycles 3 and 4. Each cycle is 21 days long. After 6 cycles, participants will start maintenance therapy of bevacizumab and atezolizumab for additional 16 cycles. |
| Placebo With Paclitaxel, Carboplatin and Bevacizumab | PLACEBO_COMPARATOR | Participants in the primary tumor-reductive surgery group will receive paclitaxel, carboplatin, atezolizumab placebo IV infusion on Day 1 of each 21-day cycle for a total of 6 cycles, and bevacizumab IV infusion starting with Cycle 2 for a total of 5 cycles, followed by maintenance therapy bevacizumab with atezolizumab placebo for a total of 22 cycles of atezolizumab placebo and 21 cycles of bevacizumab. Participants in the neoadjuvant therapy group will receive paclitaxel, carboplatin and placebo for 6 cycles and bevacizumab for 4 cycles. Interval surgery will occur between cycles 3 and 4. Each cycle is 21 days long. After 6 cycles, participants will start maintenance therapy of bevacizumab and placebo for additional 16 cycles. |
| Atezolizumab + Cobimetinib + Vemurafenib + Vemurafenib Placebo | EXPERIMENTAL | Run-In Period (Cycle 1=28 days): Participants will receive vemurafenib 960 mg (four, 240 mg tablets) PO BID along with cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21 followed by vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 22 to 28 and vemurafenib placebo (1 tablet) PO BID on Days 22 to 28. Triple Combination Period (Cycle 1 onwards): Participants will receive atezolizumab 840 mg IV infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first. |
| Atezolizumab Placebo + Cobimetinib + Vemurafenib | EXPERIMENTAL | Run-In Period (Cycle1=28 days): Participants will receive vemurafenib 960 milligrams (mg) (four, 240 mg tablets) orally (PO) twice a day (BID) along with cobimetinib 60 mg (three, 20 mg tablets) PO once a day (QD) on Days 1 to 21 followed by vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 22 to 28. Triple Combination Period (Cycle 1 onwards): Participants will receive ATZ placebo by intravenous (IV) infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, and vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first. |
| Atezolizumab + Enzalutamide | EXPERIMENTAL | Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months). |
| Enzalutamide | ACTIVE_COMPARATOR | Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months). |
| Atezolizumab+Gemcitabine+Carboplatin/Cisplatin | EXPERIMENTAL | Participants will receive blinded atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin). |
| Placebo+Gemcitabine+Carboplatin/Cisplatin | PLACEBO_COMPARATOR | Participants will receive blinded placebo matched to atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin). |
| Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed | EXPERIMENTAL | Participants received intravenous (IV) infusion of 1200 milligrams (mg) of atezolizumab on Day 1 every 3 weeks (q3w), IV infusion of 500 milligrams per meter square (mg/m\^2) pemetrexed on Day 1 q3w, and as per investigator's choice either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain area under concentration versus time (AUC) = 6 milligrams per milliliter per minute (mg/mL/min) or IV infusion of 75 mg/m\^2 cisplatin q3w on Day 1 q3w, during induction dosing period of 4 or 6 cycles (Cycle length=21 days). Participants who experienced clinical benefit during the induction phase began maintenance therapy. Participants will receive IV infusion of 1200 mg of atezolizumab and 500 mg/m\^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period. |
| Arm B (Carboplatin or Cisplatin + Pemetrexed) | ACTIVE_COMPARATOR | Participants received IV infusion of 500 mg/m\^2 pemetrexed on Day 1 q3w, and as per investigator's choice of either IV infusion of carboplatin on Day 1 q3w with a dose calculated using 'Calvert formula' to obtain AUC =6 mg/mL/min or IV infusion of 75 mg/m\^2 cisplatin q3w on Day 1 q3w, during induction dosing period for 4 or 6 cycles (Cycle length=21 days). Participants who did not experience disease progression during the induction phase began maintenance therapy. Participants will receive IV infusion of 500 mg/m\^2 of pemetrexed on Day 1 q3w until disease progression in the maintenance period. |
| Best Supportive Care | ACTIVE_COMPARATOR | Enrollment Phase: Participants will receive four 21-day cycles of cisplatin-based chemotherapy (cisplatin plus either vinorelbine or docetaxel or gemcitabine or pemetrexed \[non-squamous cell NSCLC only\]), unless unacceptable toxicity, disease relapse, or participant's decision to discontinue occur. Randomization Phase: After enrollment phase participants will receive only the best supportive care and will undergo periodic chest X-ray and CT scan. |
| Atezolizumab (MPDL3280A), an Engineered Anti-PD-L1 Antibody | EXPERIMENTAL | Atezolizumab 1200 milligrams (mg) was administered via intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first. |
| Docetaxel | ACTIVE_COMPARATOR | Docetaxel 75 milligrams per meter square (mg/m\^2) was administered via IV infusion on Day 1 of each 21-day cycle until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by sponsor, whichever occurs first. |
| Cohort A: Atezolizumab+Bevacizumab | EXPERIMENTAL | Participants will receive atezolizumab plus bevacizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator. |
| Cohort B: Atezolizumab | EXPERIMENTAL | Participants will receive atezolizumab until unacceptable toxicity or loss of clinical benefit, as determined by the investigator. |
| Arm C | EXPERIMENTAL | Participants will receive IV tobemstomig + IV tiragolumab Q3W. |
| IMM-101 plus atezolizumab | EXPERIMENTAL | One initial dose of IMM-101 intradermally at 1.0 mg 14 ±2 days before start of atezolizumab treatment (same as Arm A) |
| Arm A: Atezolizumab plus Trastuzumab with XELOX (Capecitabine + Oxaliplatin) | EXPERIMENTAL | Participants will receive atezolizumab + trastuzumab + XELOX (Capecitabine + Oxaliplatin) for 3 treatment cycles prior to surgery, each cycle is 3 weeks. Following surgery, patrticipants will receive 5 further cycles of this regimen. |
| Arm B: Trastuzumab with XELOX (Capecitabine + Oxaliplatin) | ACTIVE_COMPARATOR | Participants will receive trastuzumab + XELOX (Capecitabine + Oxaliplatin) for 3 treatment cycles prior to surgery, each cycle is 3 weeks. Following surgery, participants will receive 5 further cycles of this regimen. |
| Atezolizumab + Placebo | PLACEBO_COMPARATOR | Participants will receive atezolizumab followed by placebo Q3W on Day 1 of each 21-day cycle. |
| Arm A: Atezo+Bev+CisGem, followed by Atezo+Bev | EXPERIMENTAL | Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8. |
| Arm B: Atezo+PBO+CisGem, followed by Atezo+PBO | ACTIVE_COMPARATOR | Participants will receive atezolizumab intravenously on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. Participants will receive placebo matching bevacizumab intravenously on Day 1 of each 21-day cycle. Participants will receive cisplatin intravenously followed by gemcitabine on Days 1 and 8 of each 21-day cycle for Cycles 1-8. |
| LDRT concurrent cisplatin/carboplatin + etoposide + atezolizumab | EXPERIMENTAL | Participants will receive the following treatment regimens: LDRT concurrent cisplatin/carboplatin + etoposide + atezolizumab. Induction treatment will be administered on a 21-day cycle for four cycles. Concurrent radiation therapy will be conducted from Day 1 - Day 5 in the first cycle. Following the induction phase, participants will continue maintenance therapy with atezolizumab. Participants will be treated until loss of clinical benefit, or unaccepted toxicity, or withdrawal of consent, or death (whichever occurs first). |
| Atezolizumab plus Bevacizumab | EXPERIMENTAL | Participants will receive atezolizumab plus bevacizumab intravenously on Day 1 of each cycle. Treatment will continue until progressive disease, unacceptable toxicity, or death. |
| Atezolizumab and Bevacizumab | EXPERIMENTAL | The research study procedures include screening for eligibility, study treatment including evaluations, a biopsy, and follow up visits. * Atezolizumab will be administered intravenously at a fixed predetermined dose every three weeks * Bevacizumab will be administered intravenously at a fixed predetermined dose every three weeks, with 21 consecutive days defined as a treatment cycle. Treatment will be administered on an outpatient basis Study treatment will continue until study doctors decide to stop therapy due to criteria which may include disease progression, adverse events or changes in condition. Participants will be followed for survival health information following treatment until the study ends, which could be approximately 5 years from start of treatment |
| Breast Cohort | EXPERIMENTAL | Cohort of participants whose primary tumour type is breast. |
| Lung Cohort | EXPERIMENTAL | Cohort of participants whose primary tumour type is lung. |
| GI Cohort | EXPERIMENTAL | Cohort of participants whose primary tumour type is gastrointestinal (including pancreas and hepatobiliary). |
| GU Cohort | EXPERIMENTAL | Cohort of participants whose primary tumour type is genitourinary. |
| Gyne Cohort | EXPERIMENTAL | Cohort of participants whose primary tumour type is gynecological. |
| Sarcoma Cohort | EXPERIMENTAL | Cohort of participants whose primary tumour type is sarcoma. |
| Primary Unknown Cohort | EXPERIMENTAL | Cohort of participants whose primary tumour type is unknown. |
| Other Cohort | EXPERIMENTAL | Cohort of participants whose primary tumour type is not classified as one of the other study arms. This cohort includes participants with cancers from the head and neck, skin, or rare cancers. |
| Trastuzumab Emtansine + Atezolizumab | EXPERIMENTAL | Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion or matching Placebo followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (approximately 29 months) |
| Trastuzumab Emtansine + Placebo | ACTIVE_COMPARATOR | Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (approximately 29 months) |
| Cohort 1: Treatment-naive Cisplatin Ineligible Participants | EXPERIMENTAL | Participants with advanced disease who are treatment-naive for advanced urothelial carcinoma and cisplatin ineligible will receive atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until disease progression per RECIST v1.1 criteria or unmanageable toxicity. |
| Cohort 2: Participants With Second-line or Beyond Treatments | EXPERIMENTAL | Participants with advanced disease who had disease progression during or following treatment with at least one platinum-containing chemotherapy regimen in the metastatic setting will receive atezolizumab 1200 mg via IV infusion on Day 1 of 21-day cycles until loss of clinical benefit or unmanageable toxicity. |
| Atezo + Bev | EXPERIMENTAL | Participants in the atezolizumab plus bevacizumab (Atezo + Bev) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first. |
| Atezo + Bev +Tira | EXPERIMENTAL | Participants in the atezolizumab plus bevacizumab plus tiragolumab (Atezo + Bev +Tira) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first. |
| Tobe + Bev | EXPERIMENTAL | Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first. Enrollment is closed. |
| Atezo + Tira | ACTIVE_COMPARATOR | Participants in the atezolizumab plus tiragolumab arm will receive treatment for two cycles (6 weeks) until surgery or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. |
| Atezo + Tira + CP | EXPERIMENTAL | Participants in the atezolizumab plus tiragolumab plus carboplatin plus paclitaxel arm arm will receive treatment for two cycles (6 weeks) until surgery or until unacceptable toxicity or loss of clinical benefit, whichever occurs first. |
| Atezolizumab + Tivozanib | EXPERIMENTAL | - |
| Cohort A | EXPERIMENTAL | Participants with disease progression on or after treatment with an anti-PD-1 agent will receive cobimetinib and atezolizumab treatment during 28-day cycles. |
| Cohort B | EXPERIMENTAL | Participants with disease progression on or after treatment with an anti-PD-1 agent will receive cobimetinib prior to initiating atezolizumab treatment during Cycle 1. During subsequent 28-day cycles participants will initiate both atezolizumab and cobimetinib on Day 1 of each cycle. Participants in this cohort will undergo tumor biopsies before and during treatment. |
| Cohort C | EXPERIMENTAL | Participants with advanced melanoma, who have not received previous treatment, will receive atezolizumab monotherapy during 21-day cycles. |
| Dose-Finding Phase (Part 1): Rucaparib and Atezolizumab | EXPERIMENTAL | Approximately 6-18 participants with advanced gynecological cancers will receive different doses of rucaparib administered orally (PO) twice daily (BID) with a fixed dose of atezolizumab (1200 milligrams \[mg\] intravenously \[IV\], every 21 days) in 21-day cycles, starting with 400 mg rucaparib BID. The recommended Phase II dose (RP2D), determined by the highest dose level with an acceptable safety profile and with a minimum of 6 participants at which fewer than one-third of participants experience a DLT, was identified as 600 mg rucaparib twice a day (BID). |
| Dose-Expansion Phase (Part 2): Rucaparib and Atezolizumab | EXPERIMENTAL | Two tumor-specific expansion cohorts will begin treatment with a 21-day run-in period of rucaparib monotherapy at the specified dose for rucaparib in the potential RP2D identified in Part 1 for the combination. Cohort 1 will have approximately 30 participants with advanced, platinum-sensitive ovarian cancer with tumors harboring a tBRCA mutation \[tBCRA(mut)\] or BRCA-like molecular signature \[tBRCA(wt)/LOH(high)\]. Cohort 2 will have approximately 20 participants with previously treated triple-negative breast cancer (TNBC) with a tBRCA mutation \[tBCRA(mut)\] or BRCA-like molecular signature \[tBRCA(wt)/LOH(high)\] and have not been exposed to cancer immunotherapies. Following the run in period, participants will receive the combination of rucaparib (specified dose, BID) and atezolizumab (1200 mg IV, every 21 days) in 21-day cycles. |
| Escalation Part (Arm A): Atezolizumab, RO6874281 | EXPERIMENTAL | Participants will receive RO6874281 in combination with atezolizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has complete response (CR), treatment may be discontinued and reintroduced if progressive disease (PD), for a maximum duration of 24 months. |
| Escalation Part (Arm B): Atezolizumab, Bevacizumab, RO6874281 | EXPERIMENTAL | Participants will receive RO6874281 in combination with atezolizumab and bevacizumab until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. |
| Extension Part (Arm A): Atezolizumab, RO6874281 | EXPERIMENTAL | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: no new participants are being enrolled in the arm at this time. |
| Extension Part (Arm B): Atezolizumab, Bevacizumab, RO6874281 | EXPERIMENTAL | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab and bevacizumab once a week for 4 weeks followed by once every 2 weeks afterwards until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: no new participants are being enrolled in the arm at this time. |
| Extension Part (Arm C): Atezolizumab, RO6874281 | EXPERIMENTAL | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab once every 3 weeks until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: no new participants are being enrolled in the arm at this time. |
| Extension Part (Arm D): Atezolizumab, Bevacizumab, RO6874281 | EXPERIMENTAL | Based on the maximum tolerated dose or recommended dose as determined in the dose-escalation part, participants will receive RO6874281 in combination with atezolizumab and bevacizumab once every 3 weeks until disease progression, unacceptable toxicities, or withdrawal of consent, or as long as the participant experiences clinical benefit, or if the participant has CR, treatment may be discontinued and reintroduced if PD, for a maximum duration of 24 months. Note: Arm D is closed for future enrollment |
| Dose-Escalation Phase | EXPERIMENTAL | During the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and Pola on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1, Atezo on Day 1, and Pola on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months, during maintenance treatment for FL participants. |
| Expansion Phase | EXPERIMENTAL | For FL during the induction treatment Cycle 1 (21-day cycles): participants will receive obinutuzumab on Days 1, 8, and 15 and Pola at identified RP2D (decided from dose-escalation phase) on Day 1; Cycles 2-6: participants will receive obinutuzumab on Day 1 and Pola at RP2D on Day 1. This is followed by obinutuzumab on Day 1 of every other month starting with Month 1 for 24 months (during maintenance treatment for FL participants). |
| Safety Run-In Phase | EXPERIMENTAL | For DLBCL, during the induction treatment Cycles 1-6 (21-day cycles): participants will receive rituximab on Day 1 and Pola on Day 1. |
| Cohort A1: Safety Cohort (Relapsed/refractory AML) | EXPERIMENTAL | An initial safety evaluation of the combination will be performed in 9 participants with relapsed/refractory AML. All participants will receive atezolizumab (840 milligrams \[mg\] IV on Days 8 and 22 of every 28-day cycle) administered in combination with guadecitabine (60 milligrams per square meter \[mg/m\^2\] subcutaneously \[SC\] on Days 1-5 of every 28-day cycle). Treatment with both study drugs will continue until loss of clinical benefit (except in participants who achieve a CR, CRp, or CRi), evidence of unacceptable toxicity, voluntary withdrawal from the study, study termination, or death, whichever occurs first. Participants who achieve a CR, CRp, or CRi will receive an additional six cycles of the combination as consolidation treatment. Participants will discontinue therapy at the end of consolidation response assessment even if the CR, CRp, or CRi is maintained at that time. |
| Cohort A2: Expansion Cohort (Relapsed/refractory AML) | EXPERIMENTAL | If the combination of atezolizumab and guadecitabine is found to be safe and tolerable in Cohort A1, an expansion cohort of 11 participants with relapsed/refractory AML (Cohort A2) will be evaluated. All participants will receive atezolizumab (840 mg IV on Days 8 and 22 of every 28-day cycle) administered in combination with guadecitabine (60 mg/m\^2 SC on Days 1-5 of every 28-day cycle). Treatment with both study drugs will continue until loss of clinical benefit except in participants who achieve a CR, CRp, or CRi), evidence of unacceptable toxicity, voluntary withdrawal from the study, study termination, or death, whichever occurs first. Participants who achieve a CR, CRp, or CRi will receive an additional six cycles of the combination as consolidation treatment. Participants will discontinue therapy at the end of consolidation response assessment even if the CR, CRp, or CRi is maintained at that time. |
| Cohort A3: Safety Cohort (Previously Untreated AML) | EXPERIMENTAL | If the combination of atezolizumab and guadecitabine is found to be safe and tolerable in Cohort A1, Cohort A3 will assess the safety and tolerability of the combination in 6 participants with untreated AML, who are older and unfit for induction chemotherapy. All participants will receive atezolizumab (840 mg IV on Days 8 and 22 of every 28-day cycle) administered in combination with guadecitabine (60 mg/m\^2 SC on Days 1-5 of every 28-day cycle). Treatment with both study drugs will continue until loss of clinical benefit except in participants who achieve a CR, CRp, or CRi), evidence of unacceptable toxicity, voluntary withdrawal from the study, study termination, or death, whichever occurs first. Participants who achieve a CR, CRp, or CRi will receive an additional six cycles of the combination as consolidation treatment. Participants will discontinue therapy at the end of consolidation response assessment even if the CR, CRp, or CRi is maintained at that time. |
| Cohort A4: Expansion Cohort (Previously Untreated AML) | EXPERIMENTAL | If Cohort A3 is deemed safe and tolerable, an expansion cohort (Cohort A4) of 14 participants with untreated AML, who are older and unfit for induction chemotherapy will be evaluated. All participants will receive atezolizumab (840 mg IV on Days 8 and 22 of every 28-day cycle) administered in combination with guadecitabine (60 mg/m\^2 SC on Days 1-5 of every 28-day cycle). Treatment with both study drugs will continue until loss of clinical benefit except in participants who achieve a CR, CRp, or CRi), evidence of unacceptable toxicity, voluntary withdrawal from the study, study termination, or death, whichever occurs first. Participants who achieve a CR, CRp, or CRi will receive an additional six cycles of the combination as consolidation treatment. Participants will discontinue therapy at the end of consolidation response assessment even if the CR, CRp, or CRi is maintained at that time. |
| Cobimetinib + Bevacizumab + Atezolizumab (Stage 1: SRP) | EXPERIMENTAL | Stage 1 Safety Run-in Phase (SRP): Approximately 12 participants will receive cobimetinib 60 milligrams (mg) orally once daily for Days 1-21 with atezolizumab 840 mg and bevacizumab 5 milligrams per kilogram (mg/kg) administered by IV infusion on Days 1 and 15 of each 28-day cycle. Atezolizumab will be administered first, followed by bevacizumab, with a minimum of 60 minutes between dosing. Upon determination of the safety and tolerability of the treatment regimen, the study will proceed to Stage 2: dose expansion phase. If the results from the safety run-in phase require dose reduction in cobimetinib, then an additional Stage 1 cohort will be opened. Treatment will continue until the participant has disease progression according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first. |
| Cobimetinib + Bevacizumab + Atezolizumab (Stage 2: BC) | EXPERIMENTAL | Stage 2 Biopsy Cohort (BC): Approximately 7 evaluable participants in the biopsy cohort in expansion phase will receive bevacizumab 5 mg/kg IV on Cycle 1 Days 1 and 15 (tumor biopsy on Cycle 1 Day 8) and cobimetinib (at dose determined during safety run-in phase) orally on Cycle 1 Day 15 to Cycle 2 Day 14 (tumor biopsy on Cycle 1 Day 22). From Cycle 2 onwards, participants will follow the same treatment regimen for bevacizumab and atezolizumab (optional tumor biopsy on Cycle 2 Day 22) as those in the safety run-in phase and expansion cohort, and for cobimetinib cycles start at Day 15 and will continue 21 days to Day 7 of next cycle. Atezolizumab will be administered first, followed by bevacizumab, with a minimum of 60 minutes between dosing. Biopsies must be collected before the initiation of cobimetinib and atezolizumab. Treatment will continue until disease progression according to RECIST v1.1, unacceptable toxicity, death, decision to withdraw, or pregnancy, whichever occurs first. |
| Cobimetinib + Bevacizumab + Atezolizumab (Stage 2: EC) | EXPERIMENTAL | Stage 2 Expansion Cohort (EC): Approximately 14 participants will receive cobimetinib (at dose determined during safety run-in phase) orally once daily for Days 1-21 with atezolizumab 840 mg and bevacizumab 5 mg/kg administered by IV infusion on Days 1 and 15 of each 28-day cycle. Atezolizumab will be administered first, followed by bevacizumab, with a minimum of 60 minutes between dosing. Treatment will continue until the participant has disease progression according to RECIST v1.1, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first. |
| Cohort 1: ATZ + R-223-D (Concurrent) | EXPERIMENTAL | Participants will receive concurrent radium-223 dichloride and atezolizumab for a single-cycle, 28-day dose limiting toxicity (DLT) assessment. If the combination is initially found to be safe and tolerable, additional participants will be randomized to Arms A, B, and C. |
| RT Arm A: ATZ + R-223-D (Concurrent) | EXPERIMENTAL | If Cohort 1 regimen is found to be safe, additional participants will be randomized to this arm (randomized treatment \[RT\]) to receive concurrent radium-223 dichloride and atezolizumab. |
| RT Arm B: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In) | EXPERIMENTAL | If Cohort 1 regimen is found to be safe, additional participants will be randomized to this arm to receive radium-223 dichloride in Cycle 1 and radium-223 dichloride and atezolizumab from Cycle 2 onward. |
| RT Arm C: ATZ + R-223-D (Staggered, 28-Day ATZ Run-In) | EXPERIMENTAL | If Cohort 1 regimen is found to be safe, additional participants will be randomized to this arm to receive atezolizumab in Cycle 1 and radium-223 dichloride and atezolizumab from Cycle 2 onward. |
| Cohort 2: ATZ + R-223-D (Staggered, 28-Day R-223-D Run-In) | EXPERIMENTAL | If Cohort 1 regimen is not tolerable, Arms A, B, and C will not be introduced and additional participants will be enrolled in this cohort to receive radium-223 dichloride in Cycle 1 and radium-223 dichloride and atezolizumab in Cycle 2. If the regimen is found to be safe, additional participants will be enrolled to receive this same treatment (radium-223 dichloride in Cycle 1 and radium-223 dichloride and atezolizumab from Cycle 2 onward). If, at Cycle 2, Cohort 2 regiment is not tolerable, additional participants will be enrolled in Cohort 3. |
| Cohort 3: ATZ + R-223-D (Staggered, 56-Day R-223-D Run-In) | EXPERIMENTAL | If Cohort 2 regimen is not tolerable, additional participants will be enrolled in this cohort to receive radium-223 dichloride in Cycles 1, 2 and radium-223 dichloride and atezolizumab in Cycle 3. If the regimen is found to be safe, additional participants will be enrolled to receive this same treatment (radium-223 dichloride in Cycles 1, 2 and radium-223 dichloride and atezolizumab from Cycle 3 onward). If, at Cycle 3, Cohort 3 regiment is not tolerable, no additional participants will be enrolled in this study. |
| Atezolizumab Monotherapy: PK and Extension Phases | EXPERIMENTAL | Participants during the PK and extension phases of the study will receive atezolizumab alone at a dose of 1200 milligrams (mg) IV every 3 weeks (q3w) (in 21-day cycles) continuously until loss of clinical benefit, disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death. Study treatment may continue beyond disease progression based on the investigator's discretion. |
| Atezolizumab and Chemotherapy: Extension Phase | EXPERIMENTAL | Participants during the extension phase of the study will receive atezolizumab at a dose of 1200 mg IV on Day 1 in combination with gemcitabine at a dose of 1250 milligrams per square meter (mg/m\^2) on Days 1 and 8 and cisplatin at a dose of 75 mg/m\^2 on Day 1 (four or six 21-day cycles at the discretion of the investigator), followed by atezolizumab as a single agent at a dose of 1200 mg IV q3w on Day 1 of a 21-day cycle) as maintenance treatment continuously until loss of clinical benefit, disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death. Study treatment may continue beyond disease progression based on the investigator's discretion. |
| Phase Ia Dose-Escalation Stage: Tiragolumab | EXPERIMENTAL | Cohorts of at least 3 participants each will be treated with escalating doses of tiragolumab. |
| Phase Ia Dose-Expansion Stage: Tiragolumab | EXPERIMENTAL | Participants will be treated with tiragolumab at or below the maximum tolerated dose (MTD) or maximum administered dose (MAD) in the study. |
| Phase Ib Q3W Dose-Escalation Stage: Tiragolumab+Atezolizumab | EXPERIMENTAL | A minimum of 3 participants will be treated for each dose level of tiragolumab in combination with a fixed dose of atezolizumab with tiragolumab being administered prior to atezolizumab. |
| Phase Ib Q3W Dose-Expansion Stage: Tiragolumab+Atezolizumab | EXPERIMENTAL | Participants will be treated every 3 weeks (Q3W) with tiragolumab at or below the MTD or MAD in combination with a fixed dose of atezolizumab with tiragolumab being administered prior to atezolizumab. |
| Phase Ib Chemotherapy Dose-Expansion Stage: Cohort A | EXPERIMENTAL | In Cohort A, carboplatin or cisplatin and pemetrexed chemotherapy will be administered after atezolizumab and tiragolumab intravenous (IV) infusion. During induction phase, participants will receive atezolizumab and tiragolumab in combination with carboplatin or cisplatin and pemetrexed on Day 1 of each 21-day cycle for 4 to 6 cycles. During maintenance phase, participants will receive atezolizumab and tiragolumab in combination with pemetrexed on Day 1 of each 21-day cycle. |
| Phase Ib Chemotherapy Dose-Expansion Stage: Cohort B | EXPERIMENTAL | In Cohort B, carboplatin and paclitaxel chemotherapy will be administered after atezolizumab and tiragolumab IV infusion. During induction phase, participants will receive atezolizumab and tiragolumab in combination with carboplatin and paclitaxel on Day 1 of each 21-day cycle for 4 to 6 cycles. During maintenance phase, participants will receive atezolizumab and tiragolumab on Day 1 of each 21-day cycle (participants enrolled under protocol version 4) or Day 1 of each 28-day cycle (participants enrolled under protocol version 5). |
| Phase Ib Chemotherapy Dose-Expansion Stage: Cohort C | EXPERIMENTAL | In Cohort C, carboplatin or cisplatin and etoposide chemotherapy will be administered after atezolizumab and tiragolumab IV infusion. During induction phase, participants will receive atezolizumab and tiragolumab in combination with carboplatin or cisplatin on Day 1 of each 21-day cycle and etoposide on Day 1 to 3 of each 21-day cycle for 4 cycles. During maintenance phase, participants will receive atezolizumab and tiragolumab on Day 1 of each 28-day cycle. |
| Phase Ib Chemotherapy Dose-Expansion Stage: Cohort D | EXPERIMENTAL | In Cohort D, participants will receive atezolizumab and tiragolumab on Day 1 and capecitabine on Day 1-14 of each 21-day cycle. |
| Phase Ib Q4W Sequential Dose-Expansion Stage: Tiragolumab+Atezolizumab | EXPERIMENTAL | Participants will be treated every 4 weeks (Q4W) with fixed doses of tiragolumab and atezolizumab with tiragolumab being administered prior to atezolizumab. |
| Phase Ib Q4W Coinfusion Expansion Cohort Tiragolumab+Atezolizumab | EXPERIMENTAL | Participants will be treated Q4W with fixed doses of tiragolumab and atezolizumab mixed and administered in one IV bag. |
| Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC1 | EXPERIMENTAL | In Cohort NC1, participants will receive atezolizumab and tiragolumab in combination with bevacizumab on Day 1 of each 21-day cycle. |
| Phase Ib Non-Chemotherapy Dose-Expansion Stage: Cohort NC2 | EXPERIMENTAL | In Cohort NC2, participants will receive tiragolumab in combination with pembrolizumab on Day 1 of each 21-day cycle. |
| Arm A (Hepatocellular Carcinoma [HCC], All subtypes) | EXPERIMENTAL | Participants with advanced or metastatic and/or unresectable HCC who have received no prior treatment are non-randomized and will receive atezolizumab and bevacizumab, every 3 weeks (q3w), each cycle of 21 days, as long as participants are experiencing clinical benefit in the opinion of the investigator. |
| Arm B (Gastric Cancer) | EXPERIMENTAL | Participants with previously untreated human epidermal growth factor receptor 2 (HER2)-negative adenocarcinoma of the stomach or gastroesophageal junction (GEJ) are non-randomized and will receive atezolizumab, bevacizumab, and FOLFOX (oxaliplatin, leucovorin, and 5-fluorouracil \[FU\]), every 2 weeks (q2w), each cycle of 28 days, as long as participants are experiencing clinical benefit in the opinion of the investigator. Oxaliplatin will be administered for up to 8 cycles. After 6 months, at discretion of investigator, capecitabine may be administered as maintenance therapy without oxaliplatin instead of infusional 5-FU and leucovorin, and biologic therapy may be given every 3 weeks (q3w). In the event that a patient experiences unacceptable toxicity after replacement of infusional 5-FU and leucovorin with capecitabine, the patient may be allowed to switch back to 5-FU and leucovorin following investigator discussion with the Medical Monitor. |
| Arm C (Metastatic Pancreatic Cancer) | EXPERIMENTAL | Participants with previously untreated metastatic pancreatic cancer are non-randomized and will receive atezolizumab q2w starting on Day 1, Cycle 1 (each cycle of 28 days). Administration of nab-paclitaxel followed by gemcitabine will occur on Days 1, 8, and 15 of each cycle (3-weeks-on/1-week-off schedule). Treatment consisting of atezolizumab with gemcitabine and nab-paclitaxel may be continued as long as participants are experiencing clinical benefit in the opinion of the investigator. |
| Arm E (Randomized Metastatic Esophageal Cancer) | EXPERIMENTAL | Participants with squamous metastatic esophageal cancer (mEC) will be randomized (1:1) into Group E1 and Group E2. All participants with metastatic adenocarcinoma of esophageal carcinoma or GEJ Siewert Classification Type I will be enrolled into Group E3. In Groups E1 and E3, participants will receive atezolizumab and FOLFOX, q2w, each cycle of 28 days, as long as participants are experiencing clinical benefit in opinion of the investigator. Oxaliplatin will be administered for up to 8 cycles. In Group E2, participants will receive atezolizumab followed by cisplatin and 5-FU q3w. Cisplatin will be administered for up to 6 cycles. Treatment with atezolizumab in combination with 5-FU may be continued as long as participants experience clinical benefit in opinion of the investigator. |
| Arm F (Randomized HCC) | EXPERIMENTAL | Participants with advanced or metastatic and/or unresectable HCC who have received no prior systemic treatment will be randomized (1:1) into Group F1 and Group F2. Participants will receive atezolizumab alone (Group F2) or combined with bevacizumab (Group F1) on a q3w schedule, with dosing on Day 1 of each 21 day Cycle. Treatment with atezolizumab with or without bevacizumab may be continued as long as participants are experiencing clinical benefit in the opinion of the investigator. Participants who are randomly assigned to Group F2 (atezolizumab monotherapy) and experience investigator-assessed unequivocal radiographic progression as per RECIST v1.1 will also be given the option to cross over to atezolizumab and bevacizumab combination therapy, provided they meet the criteria for crossover and Medical Monitor approval is obtained. |
| Dose-Escalation (Part IA): RO6958688 + Atezolizumab | EXPERIMENTAL | Participants will receive RO6958688 weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 weeks (Q3W). RO6958688 dosage will not exceed the MTD if defined in the BP29541 study. |
| Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab | EXPERIMENTAL | Part IB will explore different RO6958688 administration schedules in combination with atezolizumab, consisting of: Cohort A: will compare the QW vs Q3W dosing schedules at a flat dose of RO6958688. Step Up dosing schedules: RO6958688 dose will start at 40 mg and increase with each administration up to the MTD or 1200 mg, whichever occurs first. |
| Atezolizumab-G-lena 15mg | EXPERIMENTAL | Participants were administered obinutuzumab, Atezolizumab, and 15 mg of Lenalidomide. |
| Atezolizumab-G-lena 20mg | EXPERIMENTAL | Participants were administered obinutuzumab, Atezolizumab, and 20 mg of Lenalidomide. |
| Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab | EXPERIMENTAL | Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks. |
| Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mg | EXPERIMENTAL | Participants will receive atezolizumab in combination with trastuzumab emtansine (3.6 mg/kg) every 3 weeks. |
| Cohort 1C: Atezolizumab/Trastuzumab emtansine 3.0 mg | EXPERIMENTAL | Participants will receive atezolimumab in combination with trastzumab emtansine (3.0 mg/kg) every 3 weeks. |
| Cohort 1D: Atezolizumab/Trastuzumab emtansine 2.4 mg | EXPERIMENTAL | Participants will receive atezolimumab in combination with trastzumab emtansine (2.4 mg/kg) every 3 weeks. |
| Cohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamide | EXPERIMENTAL | Participants with HER2-negative breast cancer will receive atezolizumab (every 2 weeks) in combination with doxorubicin (every 2 weeks) and cyclophosphamide for four cycles. After the completion of four cycles of combination atezolizumab /doxorubicin / cyclophosphamide, atezolizumab will be continued as a single-agent at a dose of 1200 mg every 3 weeks. |
| Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel | EXPERIMENTAL | Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks. |
| Cohort 2A: Atezolizumab/Trastuzumab/Pertuzumab | EXPERIMENTAL | Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. |
| Cohort 2B: Atezolizumab/Trastuzumab emtansine | EXPERIMENTAL | Participants will receive atezolizumab in combination with trastuzumab emtansine every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks. |
| Cohort 2C: Safety Expansion | EXPERIMENTAL | Participants with HER2-positive metastatic breast cancer/unresectable locally advanced breast cancer who received prior treatment with trastuzumab and a taxane chemotherapy will receive atezolizumab in combination with trastuzumab emtansine at the dose determined from stage 1, every 3 weeks until disease progression, lack of clinical benefit, or unacceptable toxicity. |
| Cohort 2D: Safety Expansion | EXPERIMENTAL | Participants with HER2-positive metastatic breast cancer recently progressed on an HP containing regimen will receive atezolimumab in combination with trastuzumab and pertuzumab every 3 weeks until disease progression, lack of clinical benefit, or unacceptable toxicity. |
| Atezo-G-Benda (Safety Run-In and Expansion Phases) | EXPERIMENTAL | Safety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab (G) and bendamustine during Cycle 1 (28-day cycle) and atezolizumab, obinutuzumab, and bendamustine during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (every other month \[q2m\]) for 24 months, during maintenance treatment. Expansion phase: Participants with previously untreated FL will receive same treatment regimen as described for safety run-in phase. |
| Atezo-G-CHOP (Safety Run-In Phase) | EXPERIMENTAL | Safety run-in phase: Participants with previously untreated or relapsed or refractory FL will receive obinutuzumab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, obinutuzumab, and CHOP during Cycles 2-6, during induction treatment, followed by atezolizumab (once monthly) and obinutuzumab (q2m) for 24 months, during maintenance treatment. |
| Atezo-R-CHOP (Expansion Phase) | EXPERIMENTAL | Participants with previously untreated DLBCL will receive rituximab and CHOP during Cycle 1 (21-day cycle) and atezolizumab, rituximab, and CHOP during Cycles 2-8 (atezolizumab and rituximab for 8 cycles and CHOP for either 6 or 8 cycles, as determined by the investigator), during induction treatment, followed by atezolizumab from Cycles 9-25 during consolidation treatment. |
| Cohort A: Atezolizumab - HMA R/R MDS | EXPERIMENTAL | Participants with MDS who are HMA R/R will receive atezolizumab 1200 milligrams (mg) intravenous (IV) infusion every 3 weeks (Q3W) (21-day cycle). Treatment will continue for up to 17 cycles or until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first. Participants who achieve/maintain a partial response (PR) or hematological improvement (HI) after receiving 17 cycles of therapy may continue on study treatment beyond Cycle 17 until loss of clinical benefit. |
| Cohort B: Atezolizumab+Azacitidine - HMA R/R MDS | EXPERIMENTAL | Induction: Participants with MDS who are HMA R/R will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 milligrams per square meter (mg/m\^2) subcutaneously (SC) on Days 1 to 7 of 28-day cycle, for 6 cycles. Maintenance: Participants who complete induction treatment will receive atezolizumab 1200 mg IV infusion Q3W (21-day cycle) for up to 8 additional cycles. Participants who achieve/maintain a PR or HI after completing the 8 cycles of atezolizumab maintenance therapy, may continue on study treatment until loss of clinical benefit. |
| Cohort C1: Atezolizumab+Azacitidine - HMA-Naive MDS | EXPERIMENTAL | Participants with MDS who are HMA-naive will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 mg/m\^2 SC on Days 1 to 7 of 28-day cycle, until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first. |
| Cohort C2: Atezolizumab+Azacitidine - HMA-Naive MDS | EXPERIMENTAL | If the participants enrolled in Cohort C1 fulfil the dose limiting toxicity (DLT) criteria, then additional participants with MDS who are HMA-naïve will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 mg/m\^2 SC on Days 1 to 7 of 28-day cycle, until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first. |
| Cohort A2: Atezolizumab - HMA R/R MDS | EXPERIMENTAL | If atezolizumab alone or in combination with azacitidine is found to be initially safe and tolerable in participants with HMA R/R MDS in both Cohorts A and B, then additional randomly assigned participants will receive atezolizumab 1200 mg IV infusion Q3W (21-day cycle). Treatment will continue for up to 17 cycles or until loss of clinical benefit, evidence of unacceptable toxicity, non-compliance with the protocol, voluntary withdrawal from the study, or study termination, whichever occurs first. Participants who achieve/maintain a PR or HI after receiving 17 cycles of therapy may continue on study treatment beyond Cycle 17 until loss of clinical benefit. |
| Cohort B2: Atezolizumab+Azacitidine - HMA R/R MDS | EXPERIMENTAL | If atezolizumab alone or in combination with azacitidine is found to be initially safe and tolerable in participants with HMA R/R MDS in both Cohorts A and B, then additional randomly assigned participants will receive atezolizumab 840 mg IV infusion on Days 8 and 22 of each 28-day cycle along with azacitidine 75 mg/m\^2 SC on Days 1 to 7 of 28-day cycle, for 6 cycles during induction. Participants who complete induction treatment will receive maintenance atezolizumab 1200 mg IV infusion Q3W (21-day cycle) for up to 8 additional cycles. Participants who achieve/maintain a PR or HI after completing the 8 cycles of atezolizumab maintenance therapy, may continue on study treatment until loss of clinical benefit. |
| Anti-PD-1/PD-L1 Relapsed Cohort I | EXPERIMENTAL | Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade and achieved best response of confirmed complete or partial response, or stable disease will receive GDC-0919, at the MTD or maximum administered dose (MAD) determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. |
| Anti-PD-1/PD-L1 Relapsed Cohort II | EXPERIMENTAL | Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade and achieved unconfirmed partial response or stable disease will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. |
| Biopsy Cohort A | EXPERIMENTAL | Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive GDC-0919 during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. |
| Biopsy Cohort B | EXPERIMENTAL | Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive atezolizumab during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. |
| Dose-Escalation Cohort(s) | EXPERIMENTAL | Approximately 6 to 65 participants will be enrolled and treated at escalating doses of GDC-0919 in combination with fixed-dose atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Successive groups of at least 3 participants will be evaluated during a 21-day window for DLTs, which will determine the enrollment and dosing for subsequent cohorts in the dose-escalation stage. The MTD or MAD, whichever is reached first, will be considered for the expansion stage. |
| Expansion Cohorts | EXPERIMENTAL | Approximately 160 participants (40 per diagnosis) with NSCLC, RCC, TNBC, and UBC will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with Atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. |
| Cergutuzumab+Atezolizumab (Part I) | EXPERIMENTAL | Participants will receive escalated IV doses of cergutuzumab amunaleukin in combination with atezolizumab. This is a Part I dose escalation phase of the study. Cergutuzumab amunaleukin will be escalated from a starting dose of 6 milligrams (mg) and dosing schedules of every week (qw) and every 2 weeks (q2w) may be explored. Atezolizumab will be administered in fixed flat doses of either 840 mg q2w or 1200 mg every 3 weeks (q3w). Treatment will be continued until loss of clinical benefit, unacceptable toxicities, or withdrawal of consent for a maximum treatment period of 24 months for both cergutuzumab amunaleukin and atezolizumab and may be modified if emerging data suggest longer treatment period is needed. |
| Cergutuzumab +Atezolizumab (Part II) | EXPERIMENTAL | This is a Part II expansion phase of the study. Participants will receive cergutuzumab amunaleukin at maximum tolerated dose (MTD) (or recommended dose) identified during Part I in combination with atezolizumab. Treatment will be continued until loss of clinical benefit, unacceptable toxicities, or withdrawal of consent for a maximum treatment period of 24 months for both cergutuzumab amunaleukin and atezolizumab and may be modified if emerging data suggest longer treatment period is needed. |
| Part 1 (Dose-finding): Emactuzumab + Atezolizumab | EXPERIMENTAL | Participants will receive escalating doses of emactuzumab along with atezolizumab every 3 weeks (q3w). |
| Part 2 (Expansion): Emactuzumab + Atezolizumab | EXPERIMENTAL | Participants will receive emactuzumab at or below the MTDs for the combination treatments that are determined during Part 1 along with atezolizumab. |
| Arm 1 Cohort A (Safety Evaluation):Atezolizumab + Obinutuzumab | EXPERIMENTAL | Relapsed/refractory FL and DLBCL participants will receive obinutuzumab alone on Days 1, 8, and 15 of Cycle 1 (Cycle length = 21 days), followed by atezolizumab and obinutuzumab on Day 1 of Cycles 2-8, and then atezolizumab alone on Day 1 of Cycle 9 and every cycle thereafter until unacceptable toxicities or disease progression. |
| Arm 1 Cohort B (Expansion): Atezolizumab + Obinutuzumab | EXPERIMENTAL | Relapsed/refractory FL participants will receive atezolizumab and obinutuzumab as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression. |
| Arm 1 Cohort C (Expansion): Atezolizumab + Obinutuzumab | EXPERIMENTAL | Relapsed/refractory DLBCL participants will receive atezolizumab and obinutuzumab as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression. |
| Arm 2 Cohort D (Safety Evaluation):Atezolizumab + Tazemetostat | EXPERIMENTAL | Relapsed/refractory DLBCL participants will receive atezolizumab (on Day 1) and tazemetostat (on Days 1-21) of each 21-day cycle until unacceptable toxicities or disease progression. |
| Arm 2 Cohort E (Expansion): Atezolizumab + Tazemetostat | EXPERIMENTAL | Relapsed/refractory DLBCL participants will receive atezolizumab and tazemetostat as per schedule and dose decided from the safety evaluation stage, until unacceptable toxicities or disease progression. |
| Part IA: Selicrelumab (IV) + Atezolizumab | EXPERIMENTAL | Selicrelumab at a dose of 16 milligrams (mg) will be administered intravenously (IV) on Day 1 of Cycle 1 (first cycle in this group was of 42 days, and subsequent 21-day cycles); and atezolizumab 1200 mg will be administered IV after 6 weeks on Day 1 of Cycle 2, followed by every 3 weeks during Part IA until disease progression, death, loss of follow-up, or withdrawal of consent. |
| Part IA: Selicrelumab(SC) + Atezolizumab | EXPERIMENTAL | Selicrelumab at a starting dose of 1 mg will be administered subcutaneously (SC) on Day 1 of Cycle 1 (21-day cycle) which will follow escalation in sequential cohorts; and atezolizumab 1200 mg will be administered IV on Day 1 of Cycle 2, and followed by every 3 weeks during Part IA as long as the participant experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity. |
| Part IB: Selicrelumab + Atezolizumab | EXPERIMENTAL | Selicrelumab will be administered at a starting dose of 1 mg SC on Day 2 of Cycle 1 (21-day cycle) which will follow escalation in sequential cohorts; and atezolizumab 1200 mg will be administered IV on Day 1 of Cycle 1, and followed by every 3 weeks during Part IB as long as the participant experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity. |
| Part II: Selicrelumab + Atezolizumab | EXPERIMENTAL | Atezolizumab 1200 mg will be administered IV on Day 1 of Cycle 1, and followed by every 3 weeks; and Selicrelumab will be administered at the dose defined in Part IB (not exceeding 80 mg SC \[unless IV administration in Part IB demonstrates better benefit/risk ratio\]) on Day 2 (1 day after atezolizumab administration) of every second cycle from Cycles 1 to 7, and every fourth cycle thereafter during Part II as long as the participant experiences clinical benefit in the opinion of the investigator or until unacceptable toxicity. |
| Arm A: Atezolizumab with Ipilimumab | EXPERIMENTAL | Participants will receive atezolizumab along with ipilimumab. |
| Arm B: Atezolizumab with Interferon alfa-2b | EXPERIMENTAL | Participants will receive atezolizumab along with Interferon alfa-2b. |
| Arm C: Atezolizumab with PEG- interferon alfa-2a | EXPERIMENTAL | Participants will receive atezolizumab along with PEG- interferon alfa-2a. |
| Arm D:Atezolizumab with PEG-interferon alfa-2a and Bevacizumab | EXPERIMENTAL | Participants will receive atezolizumab along with PEG- interferon alfa-2a and bevacizumab. |
| Arm E: Atezolizumab with Obinutuzumab | EXPERIMENTAL | Participants will receive atezolizumab along with obinutuzumab or atezolizumab alone. |
| Dose-Escalation: Cobimetinib, Atezolizumab | EXPERIMENTAL | Participants will receive single dose of 800 milligrams (mg) of atezolizumab IV infusion on Day 1, 15 and 29 of Cycle 1 (cycle length=42 days \[14-day run-in period + 28-day concomitant dosing period\]), thereafter with atezolizumab IV dosing every 2 weeks (q2w) in all subsequent treatment cycles (28 days each). Combination with cobimetinib will begin on Cycle 1 Day 15 and will be given at increasing dose levels during Stage 1. During Stage 1, cobimetinib will be administered once daily (QD) orally for 21 consecutive days out of 28 days (21/7 dosing schedule) at a starting dose of 20 mg with escalation of 20 mg until the maximum tolerated dose (MTD; not more than 60 mg) for the two-drug combination. |
| Dose-Expansion: Cobimetinib, Atezolizumab | EXPERIMENTAL | Participants will receive single dose of 800 mg of atezolizumab IV infusion q2w in all subsequent treatment cycles (28 days each). Participants will receive cobimetinib at the selected recommended RP2D on Days 1-14 of each 28-day cycle during Stage 2. |
| Vanucizumab | EXPERIMENTAL | Participants will receive escalating doses of vanucizumab and fixed dose of vanucizumab, intravenously every 2 weeks. |
| Vanucizumab + Atezolizumab | EXPERIMENTAL | Participants will receive fixed dose of vanucizumab along with atezolizumab, intravenously every 2 weeks. |
| Cohort 1 (C1): Ate+Vem - No Run-in | EXPERIMENTAL | Participants will receive atezolizumab (Ate) 1200 milligrams (mg) every 3 weeks (q3w) along with vemurafenib (Vem) 720 mg twice daily (BID) for 21 days in each cycle followed by 7 days off treatment (28-day cycle). Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent occurs. |
| Cohort 2 (C2): Ate+Vem (56 Day Run-in) | EXPERIMENTAL | Run-in period (56 days): participants will receive vemurafenib 960 mg orally BID from Day 1 to 49 and vemurafenib 720 mg orally BID from Day 50 to 56. Combination treatment period: Participants will receive fixed dose of atezolizumab 1200 mg intravenous (IV) q3w in combination with vemurafenib 720 mg orally BID in 21 days cycle. |
| Cohort 3 (C3): Ate+Vem (28 Day Run-in) | EXPERIMENTAL | Run-in period (28 days): participants will receive vemurafenib 960 mg orally BID for 21 days, then vemurafenib 720 mg orally BID for 7 days. Combination treatment period: Participants will receive fixed dose of atezolizumab 1200 mg IV q3w in combination with vemurafenib 720 mg orally BID in 21 days cycle. |
| Cohort 4 (C4): Ate+Vem+Cob (28 Day Run-in) | EXPERIMENTAL | Run-in period (28 days): participants will receive vemurafenib 960 mg orally BID for 21 days, then vemurafenib 720 mg orally BID for 7 days in combination with cobimetinib (Cob) 60 mg IV once daily, 21 days on/7 days off schedule (21/7). Combination treatment period: Participants will receive fixed dose of atezolizumab 800 mg IV every 2 weeks (q2w) in combination with vemurafenib 720 mg orally BID and cobimetinib 60 mg orally once daily 21/7 in 28 days cycle. |
| ECA: Ate+Vem+Cob (Mandatory Biopsy PD) | EXPERIMENTAL | Expansion Cohort A (ECA): Approximately 10 participants who experienced disease progression (PD) after receiving prior checkpoint inhibitor therapy will be enrolled and treated with atezolizumab plus (+) vemurafenib + cobimetinib. Serial biopsy tissue sample collections of accessible lesions will be mandatory for all participants enrolled in this cohort. The doses will be decided based on the results of Cohorts 1-4. |
| ECB: Ate+Vem+Cob (Mandatory Biopsy) | EXPERIMENTAL | Expansion Cohort B (ECB): Approximately 20 participants will be enrolled and treated with atezolizumab + vemurafenib + cobimetinib. Serial biopsy tissue sample collections of accessible lesions will be mandatory for all participants. The doses will be decided based on the results of Cohorts 1-4. |
| ECC: Ate+Vem+Cob (No Mandatory Biopsy) | EXPERIMENTAL | Expansion Cohort C (ECC): Approximately 10 participants who experienced disease progression after receiving prior checkpoint inhibitor therapy will be enrolled and treated with atezolizumab + vemurafenib + cobimetinib. Serial biopsy tissue sample collections will be optional for all participants enrolled in this cohort. The doses will be decided based on the results of Cohorts 1-4. |
| A: Atezolizumab + Bevacizumab | EXPERIMENTAL | Participants will receive atezolizumab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion (or a selected dose level not to exceed the single agent MTD or MAD determined in Study PCD4989g) with bevacizumab 15 mg/kg every 3 weeks (q3w). After establishment of MTD or MAD, participants will receive bevacizumab 15 mg/kg IV infusion on Day 1 of Cycle 1 followed by atezolizumab 1200 mg IV infusion q3w after Days 5-7 and then atezolizumab 1200 mg q3w and bevacizumab 15 mg/kg q3w on Day 1 of all subsequent cycles until disease progression or unacceptable toxicity. |
| B: Atezolizumab + Bevacizumab + FOLFOX | EXPERIMENTAL | Participants will receive FOLFOX IV infusion (oxaliplatin \[85 milligrams per square meter {mg/m\^2}\], leucovorin \[400 mg/m\^2\], 5-FU \[400 mg/m\^2\]) on Day 1 of Cycle 1 and then atezolizumab 800 mg IV infusion every 2 weeks (q2w), bevacizumab 10 mg/kg IV infusion q3w and FOLFOX q2w on Day 1 of all subsequent cycles as per institutional guidelines until disease progression or unacceptable toxicity. |
| C: Atezolizumab + Carboplatin + Paclitaxel | EXPERIMENTAL | Participants will receive atezolizumab 1200 mg IV infusion q3w in combination with paclitaxel 200 mg/m\^2 IV infusion q3w and then carboplatin IV q3w (on Day 1 of every 3-week cycle) to achieve an initial target area under the curve (AUC) of 6 milligrams per milliliter\*minute (mg/mL\*min) until disease progression or unacceptable toxicity. |
| D: Atezolizumab + Carboplatin + Pemetrexed | EXPERIMENTAL | Participants will receive atezolizumab 1200 mg IV infusion q3w in combination with premetrexed 500 mg/m\^2 IV infusion q3w and then carboplatin IV q3w (on Day 1 of every 3-week cycle) to achieve an initial target AUC of 6 mg/mL\*min until disease progression or unacceptable toxicity. |
| E: Atezolizumab + Carboplatin + Nab-paclitaxel | EXPERIMENTAL | Participants will receive atezolizumab 1200 mg IV infusion q3w (on Day 1 of every 3-week cycle) in combination with nab-paclitaxel 100 mg/m\^2 IV infusion once weekly (qw) (on Days 1, 8 and 15 of every 3-week cycle) and then carboplatin IV infusion q3w (on Day 1 of every 3-week cycle) to achieve an initial target AUC of 6 mg/mL\*min until disease progression or unacceptable toxicity. |
| F: Atezolizumab + Nab-paclitaxel | EXPERIMENTAL | Participants will receive atezolizumab 800 mg IV infusion q2w (Days 1 and 15) in combination with nab-paclitaxel 125 mg/m\^2 IV infusion qw (on Days 1, 8 and 15 of every 3-week cycle) until disease progression or unacceptable toxicity. |
| Dose Escalation Cohort: Atezolizumab 0.01 mg/kg | EXPERIMENTAL | Participants will receive intravenous (IV) infusion of atezolizumab 0.01 milligrams per kilogram (mg/kg) every 3 weeks (q3w) until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. |
| Dose Escalation Cohort: Atezolizumab 0.03 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of atezolizumab 0.03 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. |
| Dose Escalation Cohort: Atezolizumab 0.1 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of atezolizumab 0.1 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. |
| Dose Escalation Cohort: Atezolizumab 0.3 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of atezolizumab 0.3 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. |
| Dose Escalation Cohort: Atezolizumab 1 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of atezolizumab 1 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. |
| Dose Escalation Cohort: Atezolizumab 3 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of atezolizumab 3 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. |
| Dose Escalation Cohort: Atezolizumab 10 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of atezolizumab 10 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. |
| Dose Escalation Cohort: Atezolizumab 20 mg/kg | EXPERIMENTAL | Participants will receive IV infusion of atezolizumab 20 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. |
| Expansion Cohort (Atezolizumab) | EXPERIMENTAL | Participants will receive IV infusion of atezolizumab q3w up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. The dose which result in total drug exposure less than or equal to (\</=) exposures achieved at the MTD or maximum administered dose (MAD), will be selected for expansion cohort. |
| Name | Type | Description |
|---|---|---|
| Atezolizumab | DRUG | Atezolizumab will be administered by intravenous (IV) infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle. |
| Bevacizumab | DRUG | Bevacizumab will be administered by IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle. |
| Tiragolumab | DRUG | Tiragolumab will be administered by IV infusion at a fixed dose of 600 mg on Day 1 of each 21-day cycle. |
| Placebo | OTHER | Placebo matching tiragolumab will be administered by IV infusion on Day 1 of each 21-day cycle. |
| Pemetrexed | DRUG | Pemetrexed will be administered as directed per the parent study. |
| Paclitaxel | DRUG | Paclitaxel will be administered as directed per the parent study. |
| Enzalutamide | DRUG | Enzalutamide will be administered as directed per the parent study. |
| Trastuzumab Emtansine | DRUG | Trastuzumab emtansine will be administered at a dose of 3.6 mg/kg Q3W for 14 weeks. |
| Trastuzumab | DRUG | Trastuzumab will be used to complete 14 cycles of study treatment if trastuzumab emtansine is discontinued for toxicity not considered to be related to the trastuzumab component of the drug. |
| Lenvatinib | DRUG | Lenvatinib will be administered once daily by mouth each day of every 21-day study treatment cycle. Participants with a baseline body weight of \< 60 kg will receive a daily dose of 8 mg. Participants with a baseline body weight of ≥ 60 kg will receive a daily dose of 12 mg. |
| Sorafenib | DRUG | Sorafenib will be administered at a dose of 800 mg per day, i.e. two tablets of 200 mg swallowed by mouth twice daily (equivalent to a total daily dose of 800 mg) each day of every 21-day study treatment cycle. |
| Becavizumab | DRUG | Bevacizumab will be administered by IV infusion at a fixed dose of 15 mg/kg on Day 1 of each 21-day Cycle. |
| Transarterial chemoembolization (TACE) | DEVICE | TACE will be performed by clinical demand. |
| Cisplatin | DRUG | Cisplatin 60-80 mg/m\^2 administered by IV infusion on Day 1 of each 21-day cycle for 6 cycles. |
| Atezolizumab Matching Placebo | DRUG | Atezolizumab matching placebo administered by IV infusion, Q3W on Day 1 of each 21-day cycle. |
| Tiragolumab Matching Placebo | DRUG | Tiragolumab matching placebo administered by IV infusion, Q3W on Day 1 of each 21-day cycle. |
| Durvalumab | DRUG | Durvalumab will be administered based on weight at 10 mg/kg IV every 2 weeks (Q2W) on Days 1 and 15 of each 28-day cycle, or will be administered at a fixed dose of 1500 mg IV every 4 weeks (Q4W) (for participants whose weight \>/= 30 kg) on Day 1 of each 28-day cycle. |
| Carboplatin | DRUG | Carboplatin will be administered by IV infusion to achieve an initial target AUC of 6 mg/mL/min. |
| Matching Placebo | DRUG | Matching Placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle. |
| Nab-Paclitaxel | DRUG | Nab-Paclitaxel will be administered at the 100 mg/m2 dose via IV infusion on Days 1, 8, and 15 of every 28-day cycle. Day 8: Nab-paclitaxel may be administered on Days 8-11 of each cycle. Day 15: Nab-paclitaxel may be administered on Days 15-18 of each cycle, on the same day with the atezolizumab infusion. |
| Ipatasertib | DRUG | Ipatasertib was administered as per the dosage regimen mentioned in arm descriptions. |
| Placebo for Atezolizumab | DRUG | Placebo was administered as per the dosage regimen mentioned in arm descriptions. |
| Placebo for Ipatasertib | DRUG | Placebo was administered as per the dosage regimen mentioned in arm descriptions. |
| Etoposide | DRUG | Etoposide will be administered by IV infusion over 60 minutes following carboplatin administration, during the induction phase on Day 1 through 3 of each cycle. On Days 2 and 3, patients will receive etoposide alone. |
| Alectinib | DRUG | Alectinib will be administered as directed per the parent study. |
| Cobimetinib | DRUG | Cobimetinib will be administered as directed per the parent study. |
| Vemurafenib | DRUG | Vemurafenib will be administered as directed per the parent study. |
| FAP IL2V | DRUG | FAP IL2V will be administered as directed per the parent study. |
| Venetoclax | DRUG | Venetoclax will be administered as directed per the parent study. |
| Pembrolizumab | DRUG | Pembrolizumab will be administered as directed per the parent study. |
| Sunitinib | DRUG | Sunitinib will be administered as directed per the parent study. |
| Niraparib | DRUG | Niraparib will be administered as directed per the parent study. |
| Cabozantinib | DRUG | Cabozantinib will be administered as directed per the parent study. |
| Emactuzumab | DRUG | Emactuzumab will be administered as directed per the parent study. |
| Rucaparib | DRUG | Rucaparib will be administered as directed per the parent study. |
| Doxorubicin | DRUG | Doxorubicin will be administered as per the schedule specified in the respective arm. |
| Cyclophosphamide | DRUG | Cyclophosphamide will be administered as per the schedule specified in the respective arm. |
| Pertuzumab | DRUG | Pertuzumab will be administered as per the schedule specified in the respective arm. |
| rHuPH20 | DRUG | rHuPH20 will be administered as per the scheduled specified in the cohort for Part 1. |
| Cisplatin/Carboplatin | DRUG | Intravenous Infusion |
| Gemcitabine | DRUG | Gemcitabine 1000 mg/m2, followed by carboplatin target area under the curve (AUC) 2 mg/ml/min, both administered by IV infusion on Days 1 and 8 of each 3-week treatment cycle |
| Capecitabine | DRUG | Capecitabine 1000 mg/m2, twice daily orally on Days 1 to 14, followed by a 7-day rest period in each 3-week treatment cycle |
| Atezolizumab Placebo | DRUG | Placebo matching to atezolizumab on Day 1 of each 21-day cycle |
| Vemurafenib Placebo | DRUG | Will be administered as per the schedule described in individual arm. |
| Vinorelbine | DRUG | Participants will receive vinorelbine 30 mg/m\^2 IV on Days 1 and 8 of each of the four 21-day cycles. |
| Docetaxel | DRUG | Participants will receive docetaxel 75 mg/m\^2 IV on Day 1 of each of the four 21-day cycles. |
| Tobemstomig | DRUG | Participants will receive 600 mg IV tobemstomig Q3W. |
| Radiotherapy | RADIATION | Weeks 1-5: 45-50.4Gy in 25-28 fractions to the pelvis on Days 1-5 every week. |
| Fluorouracil | DRUG | Weeks 1-5: fluorouracil (5-FU) 225 mg/m\^2 intravenously (IV) over 24 hours 5 days/week during radiotherapy. |
| IMM-101 | DRUG | Suspension of Heat-Killed Whole Cell Mycobacterium obuense (NCTC 13365) in Borate Buffered Saline for Intradermal Injection |
| Oxaliplatin | DRUG | Oxaliplatin 130 mg/m\^2 will be administered by IV on Day 1 of a 21-day cycle. |
| Thoracic radiation therapy (TRT) | RADIATION | Participants will receive concurrent thoracic radiation therapy (TRT) treatment, in once daily fractions, 3 Gy per fraction, to a target dose of 15 Gy in 5 fractions from Day 1-Day 5 in the first cycle. |
| Tivozanib | DRUG | Subjects in both the phase Ib and phase II portions of the study will take tivozanib orally once daily on Days 1-21 of each 28 day cycle. Subjects on the phase Ib will be assigned to receive either 1.34 mg/day (Dose level 0) or 0.89 mg/day (Dose level -1). Subjects in the phase II portion of the study will receive 0.89 mg/day. |
| RO6874281 | DRUG | Arms A and B RO6874281 will be administered as an IV infusion on Days 1, 8, 15, 22, and 29, and once in 2 weeks from Day 29 onwards. Starting dose of RO6874281 will be 5 mg, and will be increased subsequently. Doses in the extension part will be based on the maximum tolerated dose determined in the escalation part. In Arms C and D, RO will be administered on Q3W schedule at the dose defined in the dose escalation part |
| Atezolizumab [TECENTRIQ] | DRUG | Atezolizumab will be administered by intravenous (IV) infusion at a flat dose of 1200 milligram (mg) every 3 weeks (Q3W) on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment. NOTE: Atezolizumab treatment has been discontinued in all participants currently on study treatment. |
| Obinutuzumab | DRUG | Obinutuzumab will be administered by IV infusion at a flat dose of 1000 mg on Days 1, 8, and 15 of Cycle 1, and on Day 1 of Cycles 2-6, given in 21-day cycles during induction treatment, and on Day 1 of every other month during maintenance treatment (1 cycle=21 days; infusion rate starts at 50 mg/hour (hr) and increases every 30 min to a maximum of 400 mg/hr). |
| Polatuzumab Vedotin | DRUG | Polatuzumab vedotin will be administered by IV infusion. For relapsed or refractory FL either 1.4 mg/kilogram (kg) or 1.8 mg/kg (dose-escalation phase) and at RP2D (dose-expansion phase) on Day 1 of Cycles 1-6 will be given in 21-day cycles during induction treatment. For relapsed or refactory DLBCL, 1.8 mg/kg will be given during run-in phase and either 1.8 mg/kg or 1.4 mg/kg during the expansion phase (1 cycle=21 days; infusion rate starts with 90 min and decreases to 30 min). |
| Rituximab | DRUG | Rituximab will be administered by IV infusion at 375 mg/m˄2 on Day 1 of Cycles 1-6 during induction treatment (1 cycle-21 days; infusion rate starts with 50 mg/hr and increases every 30 min to a maximum of 400 mg/hr). |
| Guadecitabine | DRUG | Guadecitabine 60 mg/m\^2 SC on Days 1-5 of every 28-day cycle. |
| Radium-223 Dichloride | DRUG | Radium-223 dichloride will be administered at a dose of 55 kilobecquerels per kilogram (kBq/kg) via slow IV bolus on Day 1 of each 28-day cycle for up to 6 cycles. |
| 5-FU | DRUG | 5-FU (400 mg/m\^2) will be administered as an IV bolus, followed by 2400 mg/m\^2 by continuous IV infusion over 46 (± 1) hours, q2w. |
| Leucovorin | DRUG | Leucovorin 200 mg/m\^2 L-isomer form or 400 mg/m\^2 D,L-racemic form will be administered IV over 120 (± 15) minutes, q2w. |
| RO6958688 | DRUG | RO6958688 is administered by IV infusion In Part IA: RO6958688 is administered weekly (QW) on days 1,8 and 15 of each 21-day cycle. In Part 1b: RO6958688 is administered weekly (QW) or every 3 weeks (Q3W). Cohort A: RO6958688 starting dose will be 100 mg either QW or Q3W. Step Up dose cohorts: RO6958688 starting dose will be 40mg and increase with each administration up to the MTD or 1200 mg whichever is lower. |
| Atezolizumab (MPDL3280A) [TECENTRIQ] | DRUG | Atezolizumab will be administered at a flat dose of 840 mg on Days 1 and 15 of Cycles 2 to 6, given in 28-day cycles as induction treatment and 840 mg on Days 1 and 2 of each month, given as maintenance treatment. |
| Lenalidomide | DRUG | Lenalidomide will be administered orally once daily on Days 1 to 21 of Cycles 1 to 6 (28-day cycles) during induction treatment and on Days 1 to 21 of each month during maintenance treatment. Lenalidomide will be administered at a dose of 15 or 20 mg (dose may be de-escalated to 10 mg) during induction treatment and at 10 mg during maintenance treatment. During the expansion phase, lenalidomide will be administered at the RP2D during induction treatment and at 10 mg during maintenance treatment. |
| Bendamustine | DRUG | Bendamustine will be administered at a dose of 90 milligrams per square meter (mg/m\^2) IV on Days 1 and 2 of Cycles 1-6, during induction treatment. |
| Prednisone | DRUG | Prednisone will be administered at a dose of 40 mg/m\^2 orally on Days 1-5 of Cycle 1-6/8, during induction treatment. Prednisolone may be given if prednisone is unavailable. The 40 mg/m\^2 dose of prednisone on Day 1 will be replaced by oral corticosteroids given as premedication on Day 1 of Cycle 1 (and subsequent cycles). |
| Vincristine | DRUG | Vincristine will be administered at a dose of 1.4 mg/m\^2 (maximum 2 mg) IV on Day 1 of Cycle 1-6/8, during induction treatment. |
| Azacitidine | DRUG | Participants will receive azacitidine as per the schedule described in individual cohort. |
| GDC-0919 | DRUG | Participants will receive GDC-0919 by mouth (PO) twice daily (BID), specifically every 12 hours. During the dose-escalation stage, the first cohort will receive GDC-0919 at a starting dose of 50 mg PO BID. Dosing will commence on Day -1 for Cycle 1 and follow subsequent 21-day (Days 1 to 21) dosing cycles. The dose will be modified based upon evaluation of DLTs, with single dose escalations not to exceed 2.5-fold of the previous dose. The proposed dosages for evaluation are 50, 100, 200, 400, 600, and 1000 mg PO BID. During the expansion stage, selected solid tumor types will be treated at the MTD or MAD as determined during the dose-escalation stage. |
| Cergutuzumab Amunaleukin | DRUG | Participants will receive cergutuzumab amunaleukin IV infusion at escalated doses and at different dosing schedules in Part I and at MTD (or recommended dose) in Part II. |
| Tazemetostat | DRUG | Tazemetostat 800 mg will be administered orally, twice daily, on Days 1 to 21. |
| Selicrelumab | DRUG | Selicrelumab will be administered as per the dosage regimen mentioned in respective arm descriptions. |
| Interferon alfa-2b | DRUG | Participants will receive Interferon alfa-2b 3, 5, or 10 million international units subcutaneously every other day for up to 3 doses per week. |
| Ipilimumab | DRUG | Participants will receive Ipilimumab 1, or 3 mg/kg IV, single dose, or multiple-dose regimen q3w for up to 4 cycles (Cycle = 21 days). |
| PEG-interferon alfa-2a | DRUG | Participant will receive PEG-interferon alfa-2a 180 micrograms subcutaneous injection q3w for a total of 6 cycles (Cycle = 21 days). |
| Vanucizumab | BIOLOGICAL | Participants will receive escalating doses of vanucizumab (starting dose: 3 milligram \[mg\] per kilogram) and fixed dose of vanucizumab (MTD/RP2D: 30 mg/kg), intravenously every 2 weeks. |
Inclusion Criteria: * Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants * Disease that is not amenable to curative surgical and/or loc...
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Atezolizumab is an investigational oncology drug being studied for extensive-stage small cell lung cancer, pleural mesothelioma malignant advanced, lymphoma, squamous cell carcinoma of the head and neck, acute myeloid leukemia, carcinoma, and small cell lung cancer. It is currently in Phase 1 clinical development.
Atezolizumab is a monoclonal antibody, classified as a -mab antibody. It is being developed by Roche Holding AG for use in multiple oncology indications, including lung cancer and lymphoma.
Atezolizumab is developed by Roche Holding AG, traded on the OTC market under the ticker RHHBY. The drug is currently in Phase 1 clinical trials for various oncology indications.
Atezolizumab is in Phase 1 clinical development. It is an investigational drug and has not been approved by the FDA. It is being studied across multiple cancer types, including small cell lung cancer and lymphoma.
Atezolizumab has been studied in several clinical trials. One completed trial, NCT02729896, evaluated it in relapsed or refractory follicular lymphoma and diffuse large B-cell lymphoma. Another completed trial, NCT03038100, studied it in ovarian cancer. A Phase 2 trial, NCT04677504, examined it in advanced biliary tract cancer.
Yes, Atezolizumab is also known as Atezolizumab 1200 MG/40mL Intravenous Solution. This alternative name refers to the drug's formulation and concentration for intravenous administration.