Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Alectinib · 18 trials · 20 indications
An AE is considered any unfavorable and unintended sign, symptom, or disease associated with use of study drug, whether or not considered related to study drug. Preexisting conditions that worsened during study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug is reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Adverse events of special interest are cases of potential drug-induced liver injury that include an elevated alanine transaminase (ALT) or aspartate transaminase (AST) in combination with either an elevated bilirubin or clinical jaundice and suspected transmission of an infectious agent by study drug.
Selected safety laboratory parameters include alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, alkaline phosphatase (ALP), and blood creatine phosphokinase (CPK). Any treatment-emergent abnormal laboratory result accompanied by clinical symptoms or leading to a change in study medication or requiring a change in concomitant therapy is considered clinically significant.
PFS was defined as the time (in months) from randomization to the first documentation of disease progression, as determined by the investigators, or to death from any cause, whichever occurred first.
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.
PFS was assessed as time to disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.
PFS was assessed percentage of participants with disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.
An OR is defined as the confirmed occurrence of either a Complete Response (CR) or Partial Response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 criteria (or immune related \[ir\]-RECIST or standard imaging criteria for specific disease e.g. Response Evaluation in Neuro Oncology criteria \[RANO\]). In patients with leukaemia, OR will be defined as the occurrence of CR, CRi (CR incomplete neutrophil recovery) or CRp (CR with incomplete platelet recovery). The trial will report the proportion of patients with an OR and 95% credible interval.
DCB is defined as the absence of disease progression for at least 24 weeks from the start of trial treatment according to RECIST Version 1.1 criteria (or ir-RECIST or standard imaging criteria for specific disease e.g. RANO criteria) and, where relevant (e.g. for haematological malignancies), by standard bone marrow response assessment criteria. Alternative definitions of DCB based on different time points may be pre-specified for particular sub-cohorts if 24 weeks is not clinically relevant. The trial will report the proportion of patients with a DCB and 95% credible interval.
MPR is defined as ≤ 10% residual viable tumor cells as scored by local pathologists.
Scored by local pathologists; defined as lack of any viable tumor cells on review of hematoxylin and eosin (H\&E) slides after complete evaluation of a resected lung cancer specimen including all sampled regional lymph nodes.
This efficacy objective was to evaluate the efficacy of MGT vs platinum chemotherapy in term of PFS in participants with CUP whose best response to 3 cycles of platinum induction chemotherapy was assessed CR, PR, or SD.
ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) assessed by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST), v.1.1. CR is defined as disappearance of all target and non-target lesions and no new lesions, and all pathological lymph nodes must have decreased to \<10 mm in short axis. PR is defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions.
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins. AUC 0-inf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.
AUC 0-inf = AUC from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC 0-t plus AUC t-inf.
Total alectinib = unbound alectinib plus alectinib bound to plasma proteins
AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf).
AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf).
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
AUC (0-inf) = Area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0 - t) plus AUC (t - inf).
The DLTs were defined as any which included Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or Grade 4 neutropenia continuing for greater than equal to (\>=) 7 consecutive days, non-hematological toxicity of Grade 3 or higher (excluding transient electrolyte abnormalities, diarrhea, nausea, and vomiting that recovers to Grade 2 or lower with appropriate treatment and participants having Grade 2 aspartate transaminase (AST) and/or alanine transaminase (ALT) at baseline must have Grade 3 AST/ALT for 7 days or Grade 4 AST/ALT to be considered a DLT), and adverse events (AEs) that required suspension of treatment for a total of \>=7 days which the Investigator could not rule out as been related to alectinib.
RP2D was defined as the highest dose with acceptable toxicity as determined from Phase I of the study.
Percentage of participants with objective response as assessed by IRC was defined as the percentage of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of complete response (CR) or partial response (PR) based on the RECIST v1.1 criteria. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments \>=4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% confidence interval (CI).
RP2D was to be determined based on the safety and tolerability profile of the study treatment.
DLTs were to be assessed based on the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.3 (NCI-CTCAE v 4.3). DLTs: drug-related toxicities that meet any one of the following criteria: Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 neutropenia continuing for greater than or equal to (\>/=) 7 consecutive days or neutropenic fever; Non-hematological toxicity of Grade 3 or higher; Adverse events that require interruption of treatment for a total of \>/=7 days.
Tumor response was assessed by IRC according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to less than (\<) 10 millimeters (mm). PR was defined as \>/=30 percent (%) decrease in the sum of diameters (SoD) of target lesions (taking as reference the baseline SoD). The 95% confidence interval (CI) was computed using Clopper-Pearson method.
Tumor response was assessed by IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to \<10 mm. PR was defined as \>/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD). The 95% CI was computed using Clopper-Pearson method.
| Arm | Type | Description |
|---|---|---|
| Cohort B1 | EXPERIMENTAL | Participants will receive alectinib in combination with a platinum-based chemotherapy for up to 4 cycles (cycle length = 3 weeks), followed by alectinib monotherapy for up to 2 years. |
| Cohort A1: Anaplastic Lymphoma Kinase (ALK)-positive (Alectinib Arm) | EXPERIMENTAL | Participants will receive alectinib 600 milligrams (mg) orally twice daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first |
| Cohort A1: ALK-positive (Durvalumab Arm) | ACTIVE_COMPARATOR | Participants will receive 1500 mg of intravenous (IV) durvalumab every 4 weeks (Q4W) until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first |
| Cohort A2: ROS Proto-oncogene 1 (ROS 1)-positive (Entrectinib Arm) | EXPERIMENTAL | Participants will receive entrectinib 600 mg orally once daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first. Cohort A2 has been closed to enrollment. |
| Cohort A2: ROS 1-positive (Durvalumab Arm) | ACTIVE_COMPARATOR | Participants will receive 1500 mg of IV durvalumab Q4W until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first Cohort A2 has been closed to enrollment. |
| Alectinib | EXPERIMENTAL | Participants will receive alectinib at the same dose and schedule and according to the same administration guidelines as they received at the time of discontinuation from the parent trial. |
| Crizotinib | EXPERIMENTAL | Participants will receive crizotinib at the same dose and schedule and according to the same administration guidelines as they received at the time of discontinuation from the parent trial. |
| Premetrexed/Docetaxel | ACTIVE_COMPARATOR | Participants will receive chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously. |
| Treatment Arm 01: Alectinib | EXPERIMENTAL | This alectinib treatment arm is for adult, paediatric and teenage/young adult (TYA) patients with ALK-positive cancers. |
| ALK Cohort (Enrolment Closed) | EXPERIMENTAL | Participants will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care (SOC). All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with alectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of alectinib. Enrolment Closed. |
| ROS 1 Cohort (Enrolment Closed) | EXPERIMENTAL | Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib. Enrolment Closed. |
| NTRK Cohort (Enrolment Closed) | EXPERIMENTAL | Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib. Enrolment Closed. |
| BRAF Cohort (No Participants Enrolled, Cohort Closed) | EXPERIMENTAL | Participants will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with vemurafenib plus cobimetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of of vemurafenib plus cobimetinib. Cohort closed. |
| RET Cohort (Cohort closed) | EXPERIMENTAL | Participants will receive up to 8 weeks of pralsetinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with pralsetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of pralsetinib. Cohort closed. |
| PD-L1 Cohort (Enrolment Closed) | EXPERIMENTAL | Participants with positive programmed death-ligand 1 (PD-L1) in ≥1% tumor cells will receive 4 cycles of atezolizumab neoadjuvant treatment. During neoadjuvant Cycle 1 of atezolizumab, participants will also receive low-dose stereotactic body radiation therapy (SBRT) (8 gray \[Gy\] X 3). Adjuvant treatment consists of SOC treatment as determined by the investigator, per National Comprehensive Cancer Network (NCCN) guidelines. Enrolment Closed. |
| KRAS G12C Cohort | EXPERIMENTAL | Participants will receive up to 8 weeks of divarasib as neoadjuvant treatment before undergoing surgical resection per SOC. PD-L1 negative participants whose tumors have pathological response or lack radiographic progression will be have the option of continuing divarasib alone for up to 3 years or 1-4 cycles of SOC chemotherapy followed by divarasib for 3 years as adjuvant therapy. For participants who test positive PD-L1, they will have the option to receive 1-4 cycles of SOC chemotherapy followed by atezolizumab for up to 16 cycles or SOC alone. |
| Molecularly-Guided Therapy | EXPERIMENTAL | Participants will be assigned to molecularly-guided therapy based on genomic profile. |
| Platinum-Based Chemotherapy | ACTIVE_COMPARATOR | Participants will receive platinum-based chemotherapy (Carboplatin or Cisplatin in combination with Gemcitabine or Paclitaxel). |
| Cohort A: Alectinib 600 Milligrams (mg) | EXPERIMENTAL | This cohort includes participants with anaplastic lymphoma kinase (ALK) positive NSCLC. Participants will receive alectinib 600 mg orally twice in a day (BID) until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort A is complete. |
| Cohort B: Dose Finding Phase (DFP) Alectinib | EXPERIMENTAL | This cohort includes participants with rearranged during transfection (RET) positive NSCLC. Participants may receive alectinib 900 or 1200 mg orally BID until disease progression, unacceptable toxicity, withdrawal of consent or death if the recommended phase 2 dose (RP2D) is not established in any other clinical study. Participants may receive 750 mg or 600 mg, if it is unsafe to pursue the higher starting dose. Enrollment to Cohort B is complete. |
| Cohort B: Dose Expansion Phase (DEP) Alectinib | EXPERIMENTAL | This cohort includes participants with RET positive NSCLC. Participants will receive alectinib at the RP2D established in the DFP of Cohort B or a separate clinical study. Participants will continue receiving study treatment until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort B is complete. |
| Cohort C: Atezolizumab 1200 mg | EXPERIMENTAL | This cohort includes participants with bTMB positive NSCLC. Participants will receive atezolizumab at a dose of 1200 mg administered by IV infusion every 21 days (Q21D) until disease progression, loss of clinical benefit, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort C is complete. |
| Cohort C: Pemetrexed, Cisplatin or Carboplatin | ACTIVE_COMPARATOR | This cohort includes participants with bTMB positive, non-squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Carboplatin at a dose of area under the concentration-time curve (AUC) of 5 or 6 IV or cisplatin at a dose of 75 milligrams per meter square (mg/m\^2) IV on Day 1 of each cycle combined with pemetrexed at a dose of 500 mg/m\^2 IV on Day 1 of each cycle. Pemetrexed may be continued as maintenance therapy every 21 days (Q21D) as per local standard of care. Enrollment to Cohort C is complete. |
| Cohort C: Gemcitabine, Cisplatin or Carboplatin | ACTIVE_COMPARATOR | This cohort includes participants with bTMB positive, squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Gemcitabine 1250 mg/m\^2 IV on Days 1 and 8 of every cycle and cisplatin 75 mg/m\^2 IV on Day 1 Q21D or gemcitabine 1000 mg/m\^2 IV on Days 1 and 8 of every cycle and carboplatin AUC 5 IV on Day 1 Q21D. Enrollment to Cohort C is complete. |
| Cohort D: Entrectinib 600 Milligrams (mg) | EXPERIMENTAL | This cohort includes participants with c-ros oncogene 1 positive (ROS1+) NSCLC. Participants will receive entrectinib 600 mg orally once a day (QD) until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort D is complete. |
| Cohort E: Atezolizumab, Vemurafenib, and Cobimetinib | EXPERIMENTAL | This cohort includes participants with BRAF V600 mutation. Participants will receive: atezolizumab 1680 mg IV Q4W after the run-in period; cobimetinib 60 mg orally (PO) QD on Days 1-21 of each cycle during the run-in and triple-combination periods; and vemurafenib 960 mg PO twice daily (BID) on Days 1-21 of the initial run-in period, then 720 mg PO BID on Days 1-22 of the initial run-in period and on Days 1-28 of each cycle during the triple-combination period. Enrollment to Cohort E is complete. |
| Cohort F: Atezolizumab, Bevacizumab, Carboplatin, and Pemetrexed | EXPERIMENTAL | This cohort includes participants with EGFR exon 20+ NSCLC. Participants will receive atezolizumab + bevacizumab + carboplatin + pemetrexed for 4 or 6 induction cycles (cycle = 21 days). After induction therapy, participants will continue maintenance treatment with atezolizumab + bevacizumab + pemetrexed until disease progression, unacceptable toxicity, withdrawal of consent, or death. Enrollment to Cohort F is complete. |
| Cohort G: Divarasib or Docetaxel | EXPERIMENTAL | Experimental: Cohort G: GDC-6036 or Docetaxel This cohort includes participants with KRAS G12C mutation. Participants will receive GDC-6036 PO QD or IV docetaxel Q3W (75 mg/m\^2) until disease progression or unacceptable toxicity New participants will no longer receive docetaxel. |
| Cohort Z: Natural History Cohort | NO_INTERVENTION | Participants with genomic profiles of interest that are not enrolled in the other cohorts will enter into natural history follow-up. |
| ALK-Fusion Positive | EXPERIMENTAL | Part 1 is a dose-confirmation phase to confirm the recommended phase 2 dose (RP2D). In Parts 2 and 3, participants will receive alectinib at the RP2D on Days 1-28 of each 28-day cycle |
| Alectinib: Moderate Hepatic Impairment | EXPERIMENTAL | Participants with moderate hepatic impairment (based on Child-Pugh score) will receive alectinib at a single oral dose of 300 milligrams (mg) on Day 1. |
| Alectinib: Severe Hepatic Impairment | EXPERIMENTAL | Participants with severe hepatic impairment (based on Child-Pugh score) will receive alectinib at a single oral dose of 300 mg on Day 1. |
| Alectinib: Normal Hepatic Function | EXPERIMENTAL | Participants with normal hepatic function will receive alectinib at a single oral dose of 300 mg on Day 1. |
| Stage 1: Alectinib and Atezolizumab | EXPERIMENTAL | In Stage 1, starting dose of atezolizumab will be 1200 mg IV q3w administered on Day 8 of Cycle 1 and on Day 1 (21-day cycle) of each cycle thereafter along with alectinib at a starting dose of 600 mg PO BID for 28 consecutive days during Cycle 1 and on Days 1-21 of each cycle thereafter; unless maximum tolerable dose (MTD) is exceeded. The combination will be given to treatment-naive participants with ALK-positive, locally advanced or metastatic NSCLC. |
| Stage 1: Erlotinib and Atezolizumab | EXPERIMENTAL | In Stage 1, starting dose of atezolizumab will be 1200 mg IV q3w administered on Day 8 of Cycle 1 and on Day 1 (21-day cycles) of each cycle thereafter along with erlotinib at a starting dose of 150 mg PO QD, for 28 consecutive days during Cycle 1 and on Days 1-21 of each cycle thereafter; unless MTD is exceeded. The combination will be given to participants with EGFR TKI treatment-naive, locally advanced or metastatic NSCLC. |
| Stage 2: Alectinib and Atezolizumab | EXPERIMENTAL | In Stage 2, participants received the RP2D on the basis of the MTD or maximum allowed dose (MAD) of the combination treatment established in Stage 1. Treatment-naive participants with ALK-positive, locally advanced or metastatic NSCLC will be included. |
| Stage 2: Erlotinib and Atezolizumab | EXPERIMENTAL | In Stage 2, participants received the RP2D on the basis of the MTD or MAD of the combination treatment established in Stage 1. Previously untreated (or with one prior treatment that was not an EGFR TKI), EGFR mutation positive, locally advanced or metastatic NSCLC participants will be included. |
| Group 1: Treatment A first, then Treatment B | EXPERIMENTAL | Treatment A (Fasted Treatment): Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib will be administered. Treatment B (Fed Treatment): Following an overnight fast of at least 10 hours, participants will start a high-fat, high-calorie meal 30 minutes prior to study drug administration; study participants should eat this meal in 30 minutes or less. The single 600-mg oral dose of alectinib will be administered 30 minutes after the start of the meal. Each period will be separated by at least 10 days. |
| Group 1: Treatment B first, then Treatment A | EXPERIMENTAL | Treatment B (Fed Treatment): Following an overnight fast of at least 10 hours, participants will start a high-fat, high-calorie meal 30 minutes prior to study drug administration; study participants should eat this meal in 30 minutes or less. The single 600-mg oral dose of alectinib will be administered 30 minutes after the start of the meal. Treatment A (Fasted Treatment): Following an overnight fast of at least 10 hours, a single 600-mg oral dose of alectinib will be administered. Each period will be separated by at least 10 days. |
| Group 2: Alectinib Alone, Alectinib + Esomeprazole | EXPERIMENTAL | Period 1 (Days 1 to 10): Following an overnight fast of at least 10 hours, participants will start a standardized meal and should consume the meal in 30 minutes or less. The single 600-mg oral dose of alectinib will be administered 30 minutes after the start of the meal on Day 1 of Period 1. Period 2 (Days 11 to 20): Participants will receive oral esomeprazole 40 mg once daily for 6 days (Days 11-16) in the morning after an overnight fast of at least 10 hours, and at least 1 hour before a regular breakfast; On Day 16, following an overnight fast of at least 10 hours, a single oral dose of 40 mg esomeprazole will be administered 1.5 hours prior to the start of a standardized meal. Following a standardized meal, a single oral 600 mg dose of alectinib will then be administered. |
| Cohort A | EXPERIMENTAL | There will be 3 dosing periods in the study: Period 1 (Days 1 to 7), Period 2 (Days 8 to 14), and Period 3 (Days 15 to 18). Alectinib will be administered as a 40 milligrams (mg) single oral dose on Day 1 (Period 1) and Day 15 (Period 3) with an identical standardized meal (identical meal on Day 1 and Day 15 across all participants). On Days 8 to 14 (Period 2) and Days 15 to 18 (Period 3) posaconazole will be administered as a 400-mg twice daily (BID) oral dose after a high-fat meal. The follow-up assessments will occur within 10 to 14 days after the last dose of posaconazole. |
| Cohort B | EXPERIMENTAL | There will be 3 dosing periods in the study: Period 1 (Days 1 to 7), Period 2 (Days 8 to 14), and Period 3 (Days 15 to 21). Alectinib will be administered as a single oral dose at the dose selected based on Cohort A data on Day 1 (Period 1) and Day 15 (Period 3) with an identical standardized meal (identical meal on Day 1 and Day 15 across all participants). On Days 8 to 14 (Period 2) and Days 15 to 21 (Period 3) posaconazole will be administered as a 400-mg BID oral dose after a high-fat meal. The follow-up assessments will occur within 10 to 14 days after the last dose of posaconazole. |
| Alectinib: Phase I (Dose Escalation) | EXPERIMENTAL | Participants will receive escalating doses of alectinib capsules orally until disease progression, death or withdrawal for any other reasons. |
| Alectinib (Phase II: RP2 dose) | EXPERIMENTAL | Participants will receive recommended Phase II dose as determined from Phase I until disease progression, death or withdrawal for any other reasons. |
| Name | Type | Description |
|---|---|---|
| Alectinib | DRUG | Participants will receive oral alectinib twice daily (BID) for up to 2 years. |
| Cisplatin | DRUG | Participants will receive intravenous (IV) cisplatin on Day 1 of each cycle for up to 4 cycles (cycle length = 3 weeks). |
| Carboplatin | DRUG | Participants will receive IV carboplatin on Day 1 of each cycle for up to 4 cycles (cycle length = 3 weeks). |
| Pemetrexed | DRUG | Participants will receive IV pemetrexed on Day 1 of each cycle for up to 4 cycles (cycle length = 3 weeks). |
| Entrectinib | DRUG | Participants will receive oral entrectinib once daily, with or without food. |
| Durvalumab | DRUG | Participants will receive durvalumab, IV Q4W. |
| Crizotinib | DRUG | Crizotinib capsules 250 mg BID orally until no further clinical benefit is to be expected, unacceptable toxicity, availability of commercial supply, withdrawal of consent, or death, whichever occurs first. |
| Docetaxel | DRUG | Participants will receive docetaxel at a dose of 75 mg/m\^2 of body surface area intravenously every 3 weeks, until disease progression, unacceptable toxicity, withdrawal of consent or death. |
| Vemurafenib | DRUG | Participants will receive oral vemurafenib BID. |
| Cobimetinib | DRUG | Participants will receive oral cobimetinib daily. |
| Pralsetinib | DRUG | Participants will receive oral pralsetinib daily. |
| Atezolizumab | DRUG | Atezolizumab will be administered by intravenous (IV) infusion. |
| SBRT | DRUG | Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab. |
| Resection | PROCEDURE | Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC. |
| Chemotherapy | DRUG | Participants will receive SOC chemotherapy as determined by the treating physician. |
| Divarasib | DRUG | Participants in the KRAS G12C cohort will receive oral divarasib for approximately 8 weeks until the day before surgery as neoadjuvant therapy up to 3 years as adjuvant therapy. |
| Vismodegib | DRUG | Vismodegib will be administered orally at the label-recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months). |
| Ipatasertib | DRUG | Ipatasertib will be administered orally at the label-recommended dose (400 mg) once daily on Days 1-21 of each 28-day Cycle in combination with paclitaxel, and as monotherapy after the final administration of paclitaxel, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months). |
| Olaparib | DRUG | Olaparib will be administered orally at the label-recommended dose (400 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months). |
| Erlotinib | DRUG | Erlotinib will be administered orally in combination with Bevacizumab at the label recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months) |
| Bevacizumab | DRUG | Bevacizumab will be administered intravenously at 15mg/kg every 3 weeks in combination with Erlotinib until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months) |
| Trastuzumab Subcutaneous (SC) | DRUG | Trastuzumab will be administered subcutaneously, 600 mg every 3 weeks, in combination with Pertuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months) |
| Pertuzumab | DRUG | Pertuzumab will be initially be administered intravenously, 840 mg, followed by 420 mg every 3 weeks, in combination with Trastuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months) |
| Paclitaxel | DRUG | Paclitaxel will be administered intravenously, 175 mg/m\^2, once every 3 weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Carboplatin, Ipatasertib, Atezolizumab, Pertuzumab, and Trastuzumab SC |
| Gemcitabine | DRUG | Gemcitabine will be administered intravenously, 1000 mg/m\^2, twice every three weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Cisplatin, Carboplatin, Atezolizumab, Pertuzumab, and Trastuzumab SC. |
| Ivosidenib | DRUG | Ivosidenib will be administered orally at the label-recommended dose (500mg) once daily across a 28-day treatment cycle until loss of clinical benefit or unacceptable toxicity. |
| Pemigatinib | DRUG | Pemigatinib will be administered orally at the label-recommended dose (13.5mg) once daily across a 21-day treatment cycle until loss of clinical benefit or unacceptable toxicity. |
| Esomeprazole | DRUG | Esomeprazole 40 mg will be administered orally once daily for 6 days prior to alectinib administration. |
| High Fat and Calorie Meal | OTHER | High fat and calorie meal served prior to alectinib administration |
| Standard Meal | OTHER | Standard meal served prior to alectinib administration |
| Posaconazole | DRUG | Posaconazole will be administered as a 400-mg BID oral dose after a high-fat meal on Days 8 to 14 (Period 2) and Days 15 to 18 or 21 (Period 3). |
Inclusion Criteria: * Complete resection of the primary NSCLC with negative margins * Confirmed stage II to select stage IIIB (T3N2) NSCLC of non-squamous (adenocarcinoma) histology * Eastern cooperative oncology group (ECOG) performance status of 0 or 1 * Documented ALK fusion Exclusion Criteria:...
Alectinib is an investigational small molecule being studied for use in hepatic impairment, neoplasms, non-small cell lung cancer, ALK fusion-positive solid or CNS tumors, and non-small-cell lung carcinoma. It is also studied in healthy volunteers for pharmacokinetic trials. It is developed by Roche Holding AG (RHHBY).
Alectinib is a kinase inhibitor, belonging to the -tinib class of drugs. It is being studied in cancers with anaplastic lymphoma kinase (ALK) fusion positivity, including non-small cell lung cancer and solid or CNS tumors. Its mechanism involves targeting kinase activity relevant to these ALK-positive malignancies.
Alectinib is developed by Roche Holding AG, which trades under the ticker RHHBY. The company is conducting clinical trials of this investigational small molecule in oncology indications, including non-small cell lung cancer and other ALK-positive tumors.
Alectinib is in Phase 1 clinical development. It is investigational and not yet approved. The drug has completed Phase 1 and Phase 3 trials, with active trials ongoing. It is not FDA approved based on available data.
Alectinib has 8 total trials, with 3 active and 5 completed. Key completed trials include NCT01984229 and NCT02023125 in healthy volunteers, NCT02838420 in ALK-positive NSCLC, and NCT03194893, a rollover study in ALK-positive or RET-positive cancer. Total enrollment across trials is 1786.
Yes, Alectinib is also known as RO5424802. Clinical trial titles, such as NCT01984229 and NCT02023125, refer to Alectinib as RO5424802. Both names refer to the same investigational drug developed by Roche.