Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication TRODELVY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: Locally Advanced or Metastatic Breast Cancer Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. FDA label
Also known as Sacituzumab Govitecan-hziy, Sacituzumab Govitecan-hziy (SG), Sacituzumab Govitecan (SG), Trodelvy, IMMU-132, RO7445735
Sacituzumab govitecan · 46 trials · 71 indications
no invasive tumour in breast and lymph nodes (ypT0/is and ypN0)
time from date of first diagnosis to any invasive breast cancer event, death or secondary malignancy according to STEEP 2.0 criteria
ORR is defined as the number of patient with at least a confirmed complete response (CR) or partial response (PR), based on the best objective response values while on treatment
EFS after 36 months defined as time from registration to any invasive breast cancer event, death, or secondary malignancy (same definition as iDFS) according to STEEP 2.0 criteria \[103\]
EFS after 36 months defined as time from registration to any invasive breast cancer event, death, or secondary malignancy or local progress precluding surgery in neoadjuvant treated patients
pCR defined as no invasive disease in breast and lymph nodes (ypT0/is, ypN0) in patients of both arms
OS is defined as length of time from randomization until the date of death from any cause.
PFS, defined as the time from the date of randomization until the date of objective progressive disease (PD), as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST v1.1), or death from any cause, whichever comes first.
PFS is defined as time from date of randomization until the date of first objective progressive disease (PD) or death from any cause, whichever comes first.
iDFS is defined as the time from the date of randomization to death from any cause or one of the following events (whichever occurs first): invasive local, regional, or distant recurrence, invasive contralateral breast cancer.
PFS is defined as the time from the date of randomization until the date of objective progressive disease (PD) or death (whichever comes first).
PFS is defined as from the date of randomization until the date of disease progression (PD) or death, whichever occurs earlier. Disease progression will be determined according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) by Independent Reviewing Committee (IRC).
iDFS is defined as time from randomization until first iDFS event: local invasive recurrence following mastectomy, local invasive recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral invasive breast cancer, second non-breast primary cancer (excluding squamous or basal cell carcinoma of the skin), or death from any cause. (according to Hudis (J Clin Oncol 2007) ) There will be one interim analysis for efficacy after 2/3 of the events to allow for early stopping of the trial due to overwhelming efficacy.
PFS was defined as the time from the date of randomization to the date of the first documentation of disease progression or death (whichever occurred first) according to BICR using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Disease progression was defined as an increase of greater than 20% in the sum of the longest diameter (LD) of target lesions and a 5 mm absolute increase, taking as a reference the smallest sum LD recorded since the baseline assessment or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate.
PFS was defined as the time from randomization until objective tumor progression by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death, whichever came first. The date of progression was date of the last observation or radiological assessment of target lesions that either showed a predefined increase (greater than or equal to \[≥\] 20%) in the sum of the target lesions or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate.
Objective response is defined a confirmed overall response of complete response (CR) or partial response (PR) as assessed by RECIST v1.1. The objective response rate (ORR) will be estimated number of evaluable patients with a documented objective response divided by the total number of evaluable patients.
To evaluate the rate of disease control at 12 weeks for patients with extensive stage small cell lung cancer treated with Sacituzumab govitecan (SG) plus atezolizumab or durvalumab as maintenance therapy after induction treatment with chemotherapy and immunotherapy. Disease Control at 12 weeks is defined as a best response by RECIST 1.1 of CR, PR, non-CR, non-PR, or stable disease assessed by RECIST 1.1 and reported within 12 weeks (+/- 2 weeks) from the initiation of study therapy. Participants not known to have disease control at 12 weeks will be coded as lacking disease control.
The rate of patients with grade ≥ 2 diarrhea is defined as the number of patients with diarrhea grade 2 to 5 the first 2 cycles of treatment by the number of patients in the analysis set per 100. The adverse events will be assessed by the Investigator and with severity determined using defined and graded according CTCAE v.5.0. The adverse events without the severity grade reported will be considered as grade 3.
The rate of patients with grade ≥ 3 neutropenia is defined as the number of patients with neutropenia grade 3 to 5 the first 2 cycles of treatment by the number of patients in the analysis set per 100. The adverse events will be assessed by the Investigator and with severity determined using defined and graded according CTCAE v.5.0. The adverse events without the severity grade reported will be considered as grade 3.
Number and identification of altered/mutated genes in the tumors in the subgroup of patients with a longer PFS on SG post T-DXd compared to the tumors in the subgroup of patients with a shorter PFS on SG post T-DXd.
clinical evidence of new or progressing nodal or any distant metastatic disease, radical cystectomy, or death due to any cause from date of inclusion to the first documentation of a EFS event. Patients last known to be EFS event-free are censored at the date of last event-free cystoscopy and/or CT scan. Those patients without disease assessment who are still alive will be censored at date of inclusion in the trial
To determine investigator-assessed disease-free survival (DFS) at 6 months.
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR).
Hair loss rate defined as CTCAE v5.0 alopecia grade 1 or higher compared in the scalp cooling group using the Paxman Hair Loss Prevention System (PSCS) and group not using scalp cooling.
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR).
Compare the progression-free survival (PFS) of sacituzumab govitecan with pembrolizumab to that of sacituzumab govitecan alone. PFS is defined as the time from study randomization to disease progression, according to RECIST 1.1 or medical judgment, the latter based on established clinical parameters, such as rising tumor markers and physical exam evidence of progression, i.e. worsening chest wall disease, or death due to any cause, whichever occurred first. Patients alive without disease progression are censored at the date of last disease evaluation.
Compare PFS of patients randomized to receive sacituzumab govitecan in combination with pembrolizumab (Arm A) versus those randomized to receive sacituzumab govitecan monotherapy (Arm B). Defined as the time from study randomization to disease progression, per RECIST 1.1 or medical judgment, the latter based on established clinical parameters, such as rising tumor markers and physical exam evidence of progression, i.e. worsening chest wall disease, or death due to any cause, whichever occurred first.
ORR was defined as the percentage of participants who had the best overall response of either complete response (CR) or partial response (PR). Responses are based on the investigator-assessed tumor response using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria for each histologic cohort. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; PR: \>30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. The ORR rate was calculated with a two-sided exact 95% CI using the Clopper-Pearson method. Percentages are rounded off.
BORR is defined as the percentage of patients achieving complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and will be reported for each arm along with 95% two-sided confidence intervals.
Subjects who achieve ≥50% PSA decline at or before 9 weeks of therapy with Sacituzumab Govitecan (IMMU-132) are considered to have responded. PSA responses will be analyzed by descriptive statistics and summarized in tabular format (frequency tables). The overall PSA response rate will be reported along with the corresponding 95% confidence interval which will be constructed using the Wilson score method.
Proportion of participants remaining alive and progression free (using Prostate Cancer Working Group 2 (PCWG2) criteria) 6 months from time of starting treatment as estimated by the Kaplan-Meier method.
ORR will be defined as the rate of the best overall response as Complete Response (CR) or Partial Response (PR) and based on central review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria.
PFS will be defined as the time from first dose until objective tumor progression, as assessed based on central review, or death, whichever comes first.
ORR will be defined as the rate of the best overall response as Complete Response (CR) or Partial Response (PR) and based on investigator review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria.
The Maximum Tolerated Dose (MTD) in mg of Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) in Combination is assessed.
Treatment-Related Adverse Events are assessed by CTCAE v5.0 when administering Sacituzumab Govitecan (SG) and Enfortumab Vedotin (EV) in combination.
Study SG + EV combination to further refine the recommended dose and to assess the ORR (unconfirmed CR or PR) per RECIST Version 1.1 as determined by investigator for the combination of EV and SG in combination in patients with mUC progressing on platinum-based chemotherapy and PD1/L1 inhibitors.
Study SG + EV + Pembrolizumab in combination to assess the ORR (unconfirmed CR or PR) per RECIST Version 1.1 as determined by investigator for the combination therapy of Pembrolizumab in combination with EV and SG in treatment-naïve patients with mUC.
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks after initial documentation of response as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
PFS is defined as the time from the date of the first SG dose until the date of progressive disease (PD) as assessed by the investigator according to RECIST Version 1.1, or death from any cause, whichever occurs first.
The RP2D of Debio 0123 when used in combination with Sacituzumab govitecan will be determined based upon evaluation of dose-limiting toxicities (DLTs), adverse events (AEs) and other available data from secondary endpoints.
ORR, defined as the rate of patients with complete response (CR) or partial response (PR), as determined locally by the investigator using RECIST v.1.1 in patients with TNBC and HR+/HER2- advanced/metastatic breast cancer.
To establish the safety, tolerability, and feasibility of bladder preservation therapy treatment with concurrent SG and adaptive image-guided radiation therapy for patients with localized MIBC. This will be assessed by estimating the rate of acute dose-limiting toxicities occurring during Cycles 2-3 of treatment.
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR), confirmed at least 4 weeks later as assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as assessed by Independent Review Committee (IRC).
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) confirmed at least 4 weeks later as assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Cmax will be determined for 2 analytes: Free SN-38 and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. Cmax is defined as the maximum observed concentration obtained directly from the observed concentration-time data.
AUC 0-168 will be determined for 2 analytes: Free SN-38 and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-168 is defined as area under the serum concentration-time curve from time 0 to 168 hours.
Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.03. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population.
Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP).
Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP).
ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by ICR assessment according to RECIST1.1. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to \<10 mm. PR was defined as ≥ 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only.
ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by local assessment. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to \<10 mm. PR was defined as ≥3 0% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by Local Assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Levels of SN-38 and its metabolites will be measured and a ratio calculated relative to the serum concentration of SN-38 and its metabolites. The ratio will show the amount of investigational product that crosses the blood brain barrier to reach the tumor.
| Arm | Type | Description |
|---|---|---|
| Neoadjuvant treatment: 12 weeks (4 cycles) SG i.v. | EXPERIMENTAL | * Cohort 1a: In case of (near) cCR: end of treatment, followed by surgery * Cohort 1b: In case of cPR after 12 weeks: further 6 weeks (2 cycles) SG i.v., followed by surgery (use of core biopsy is allowed per investigator´s decision, if further NACT is planned) pCR dependent post-neoadjuvant treatment * In case of pCR: no further systemic treatment * In case of non-pCR: chemotherapy according to investigators decision, e.g., AC/EC q3w x 4, PAC/Carbo q1w x 12 |
| Neoadjuvant treatment: 12 weeks (4 cycles) SG+PEM i.v. | EXPERIMENTAL | * Cohort 2a: In case of (near) cCR: end of treatment, followed by surgery * Cohort 2b: In case of cPR after 12 weeks: 6 weeks (2 cycles) SG+PEM i.v., followed by surgery (use of core biopsy is allowed per investigator´s decision, if further NACT is planned) pCR dependent post-neoadjuvant treatment * In case of pCR: no further systemic treatment * In case of non-pCR: chemotherapy according to investigators decision, e.g., AC/EC q3w x 4, PAC/Carbo q1w x 12 |
| Single arm receiving sacituzumab govitecan | EXPERIMENTAL | - |
| Cohort I (non-randomized) | OTHER | Cohort I will include patients with clinical stage II disease at baseline who have a cCR after up to 12 weeks of NACT with CARBO/PAC and PEM. After surgery, patients with a pCR (ypT0/is, ypN0) will not receive further chemotherapy (CTx) but continue on SoC treatment according to current valid treatment guidelines for breast cancer at investigator´s discretion. Patients with residual disease should be considered for postoperative SoC treatment, which may include further CTx (e.g., AC/EC x 4, q2w or q3w or Capecitabine) plus PEM or Olaparib (in patients with gBRCA mutations) according to current valid treatment guidelines for breast cancer and per investigator´s discretion. |
| Cohort II (randomized) - Sacituzumab govitecan + pembrolizumab (SG+PEM) | EXPERIMENTAL | neoadjuvant SG+PEM (4 cycles), followed by surgery and pCR-dependent post-neoadjuvant SoC treatment according to current valid treatment guidelines for breast cancer and per investigator´s discretion. |
| Cohort II (randomized) - Standard-of-care chemotherapy + pembrolizumab (SoC CTx+PEM) | ACTIVE_COMPARATOR | SoC, e.g., AC x 4 + PEM or EC x 4 + PEM, followed by surgery and pCR-dependent post-neoadjuvant SoC treatment, e.g., AC x 4 \* PEM or EC x 4 + PEM, or Capecitabine + PEM or Olaparib (in patients with gBRCA mutations), according to current valid treatment guidelines for breast cancer and per investigator´s discretion. |
| Treatment Group A: SG | EXPERIMENTAL | Participants assigned to treatment group A will receive SG 10 mg/kg intravenous (IV) infusion on Days 1 and 8 of a 21-day cycle. Participants will receive study drug until progressive disease (PD), death, unacceptable toxicity, or another treatment discontinuation criterion is met. |
| Treatment Group B: Topotecan, or Lurbinectedin, or Amrubicin | EXPERIMENTAL | Participants assigned to Treatment Group B will receive one of the following investigator selected treatments within a 21 day cycle: * Topotecan 1.5 mg/m² administered daily on Days 1 through 5, or * Lurbinectedin 3.2 mg/m² administered as an intravenous infusion on Day 1 (in countries/regions where lurbinectedin is approved and available). In Japan, participants assigned to Treatment Group B may alternatively receive: • Amrubicin (available only in Japan) 40 mg/m² administered daily on Days 1 through 3 of a 21 day cycle. Study treatment will continue until disease progression, death, unacceptable toxicity, or another protocol defined criterion for treatment discontinuation is met. |
| Sacituzumab Govitecan (SG) | EXPERIMENTAL | Participants will receive SG at a dose of 10 mg/kg on Days 1 and 8 of a 21-day cycle. |
| Treatment of Physician's Choice (TPC) | ACTIVE_COMPARATOR | Participants will receive one of the following TPC, regimens determined prior to randomization. * Doxorubicin 60 mg/m\^2 IV on Day 1 of a 21-day cycle * Paclitaxel 80 mg/m\^2 IV on Days 1, 8, and 15 of a 28-day cycle |
| Sacituzumab Govitecan-hziy (SG) | EXPERIMENTAL | Participants will receive SG at a dose of 10 mg/kg infusion on Days 1 and 8 of a 21-day cycle. |
| Sacituzumab govitecan-hziy (SG) + Pembrolizumab | EXPERIMENTAL | Participants will receive SG 10 mg/kg intravenously on Days 1 and 8 of 21-day cycles and pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cycles. Treatment will be administered until a maximum of 8 cycles, local or distant disease recurrence, unacceptable toxicity, physician decision, consent withdrawal, or death. |
| Treatment of Physician's Choice (TPC): Pembrolizumab or Pembrolizumab + Capecitabine | ACTIVE_COMPARATOR | Participants will receive one of the following TPC regimens determined prior to randomization: * Pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles for 8 cycles OR * Pembrolizumab 200 mg intravenously on Day 1 of 21-day cycles and capecitabine 1000 mg/m\^2 orally twice daily on Days 1 through 14 of 21-day cycles for 8 cycles. Treatment will be administered until a maximum of 8 cycles, local or distant disease recurrence, unacceptable toxicity, physician decision, consent withdrawal, or death. |
| Pembrolizumab + Treatment of Physician's Choice (TPC) | ACTIVE_COMPARATOR | Participants will receive pembrolizumab 200 mg on Day 1 of each 21-day cycle (maximum 35 cycles) plus TPC determined prior to randomization from 1 of the 3 allowed regimens: * Paclitaxel 90 mg/m\^2 on Days 1, 8, and 15 of 28-day cycles * nab-Paclitaxel 100 mg/m\^2 on Days 1, 8, and 15 of 28-day cycles * Gemcitabine 1000 mg/m\^2 + carboplatin area under the curve (AUC) 2 on Days 1 and 8 of 21-day cycles |
| Docetaxel | ACTIVE_COMPARATOR | Participants will receive docetaxel 75 mg/m\^2 on Day 1 of a 21-day cycle (ie, once every 3 weeks) until PD, death, unacceptable toxicity, or another treatment discontinuation criterion is met. |
| Treatment of Physician's Choice | ACTIVE_COMPARATOR | Participants will receive 1 of 3 standard-of-care chemotherapeutic options, as determined by the investigator prior to randomization, and will continue to receive the same treatment for the duration of the study until disease progression, unacceptable toxicity, withdrawal of consent, or another treatment discontinuation criterion is met. Paclitaxel 175 mg/m\^2 IV on Day 1 of every 21-day cycle or Docetaxel 75 mg/m\^2 IV on Day 1 of every 21-day cycle or Vinflunine 320 mg/m\^2 IV on Day 1 of every 21-day cycle (in countries where vinflunine was approved and was commercially available). |
| Sacituzumab Govitecan-hziy | EXPERIMENTAL | Participants will receive Sacituzumab Govitecan-hziy 10 mg/kg on Days 1 and 8 of a 21-day cycle. |
| Sacituzumab govitecan | EXPERIMENTAL | Sacituzumab govitecan is administered intravenously 10 mg/kg body weight on days 1, 8 q3w for eight cycles. |
| Treatment of physician´s choice | OTHER | TPC, defined as capecitabine or platinum-based chemotherapy for eight cycles or Observation. |
| Sacituzumab | EXPERIMENTAL | - |
| Sacituzumab Govitecan + Trastuzumab (or Biosimilar) | EXPERIMENTAL | Participants will complete the following: * Baseline visit with assessments. * CT or MRI scans every 9 weeks for 27 weeks and then every 12 weeks. * Echocardiogram or MUGA scan every 12 weeks for 24 weeks and then every 16 weeks. * Cycle 1 through Cycle 2: * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily. * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily. * Cycle 2: * Day 1: Optional tumor biopsy * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily. * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily. * Cycle 3 through End of Treatment: * Days 1 and 8 of 21 day cycle: Predetermined dose of Sacituzumab govitecan 1x daily. * Day 1 of 21 day cycle: Predetermined dose of Trastuzumab either intravenously or subcutaneously 1x daily. * End of treatment: * Follow up visits every 6 months. |
| SG and atezolizumab/durvalumab | EXPERIMENTAL | Sacituzumab govitecan 10 mg/kg via IV infusion on Day 1 and Day 8 of a 21-day cycle (ie, 2 weekly doses plus 1 week without treatment) AND Atezolizumab 1200mg via IV infusion on Day 1 of a 21-day cycle (ie, once every 3 weeks) OR Sacituzumab govitecan 10 mg/kg via IV infusion on Day 1 and Day 8 of a 21-day cycle (ie, 2 weekly doses plus 1 week without treatment) AND Durvalumab 1500mg via IV infusion on Day 1 of a 21-day cycle (ie, once every 3 weeks) |
| Sacituzumab govitecan, 10 mg/kg | EXPERIMENTAL | Sacituzumab govitecan, 10 mg/kg for the first 2 weeks of 21-day cycle until progression or adverse effects prohibit further treatment |
| Sacituzumab Govitecan + Loperamide + G-CSF | EXPERIMENTAL | Upon meeting all selection criteria, patients enrolled in the study will receive the combination of: Sacituzumab govitecan :10 mg/kg, intravenously (IV) on Days 1 and 8 every 21-day cycle . This treatment will continue until disease progression, unacceptable toxicity, or physician's/patient's decision. Loperamide : 2 mg orally (PO), twice a day (BID), or 4 mg once a day (QD) during three consecutive days after administration of sacituzumab govitecan, (D2, D3, D4 and D9, D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician). G-CSF : 30 MU subcutaneously (SC) QD during two consecutive days, 48 hours after administration of sacituzumab govitecan (D3, D4 and D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician). |
| Sacituzumab Govitecan + Zimberelimab | EXPERIMENTAL | patients will be treated with Sacituzumab Govitecan 1,8q21 plus + Zimberelimab q21 for 3 cycles then radiological imaging and TURB will be repeated and patients with Stability of disease or down staging will continue Zimberelimab until disease progression, or unacceptable toxicities or completion of treatment (16 cycles). Patients with progressive disease after 3 cycles of study intervention will be treated as per clinical practice. |
| Sacituzumab Govitecan PLUS Nivolumab | EXPERIMENTAL | Patients eligible for this study treatment will receive combination therapy with Sacituzumab Govitecan with Nivolumab for 4 cycles, followed by single-agent Nivolumab for an additional 11 cycles. |
| Experimental | EXPERIMENTAL | Sacituzumab govitecan (10 mg/kg) administered intravenously on Days 1 and 8 of a 21-day cycle. Patients will be treated until progression, death, study withdrawal, or unacceptable toxicity. |
| Sacituzumab Govitecan (SG) Infusion | EXPERIMENTAL | SG will be administered on Days 1 and 8 of continuous 21-day cycles at 10 mg/kg via intravenous (IV) infusion until disease progression or unacceptable toxicity. |
| Sacituzumab Govitecan-hziy (SG) + Pembrolizumab (Cohort A) | EXPERIMENTAL | Participants assigned to Cohorts A according to tumor proportion score (TPS) status will receive SG 10 mg/kg on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle. |
| SG + Pembrolizumab (Cohort B) | EXPERIMENTAL | Participants assigned to Cohorts B according to TPS status will receive SG 10 mg/kg on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle. |
| SG + Pembrolizumab + Carboplatin Safety Run-in | EXPERIMENTAL | Participants will receive SG (de-escalating dose levels: 10.0 mg/kg, 7.5 mg/kg, or 5.0 mg/kg) on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle + carboplatin area under the concentration versus time curve (AUC)5 on Day 1 of a 21-day cycle. |
| SG + Pembrolizumab + Cisplatin Safety Run-in (Optional) | EXPERIMENTAL | Participants will receive SG (either 10 mg/kg or 7.5 mg/kg) on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle + cisplatin 75 mg/m\^2 on Day 1 of a 21-day cycle. |
| SG + Pembrolizumab + Carboplatin or Cisplatin (Cohort C) | EXPERIMENTAL | Participants assigned to Cohort C according to disease status will receive SG RP2D as determined during the safety run-in cohorts on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle + carboplatin AUC5 or cisplatin 75 mg/m\^2 as determined during the safety run-in cohorts on Day 1 of a 21-day cycle. |
| SG + Pembrolizumab + Carboplatin or Cisplatin (Cohort D) | EXPERIMENTAL | Participants assigned to Cohort D according to disease status will receive SG RP2D as determined during the safety run-in cohorts on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle + carboplatin AUC5 or cisplatin 75 mg/m\^2 as determined during the safety run-in cohorts on Day 1 of a 21-day cycle. |
| SG + Pembrolizumab + Cisplatin (Cohort E) | EXPERIMENTAL | Participants assigned to Cohort E will receive SG RP2D, as determined following safety review of Cohorts C and D, on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle + cisplatin 75 mg/ m\^2 on Day 1 of a 21-day cycle. |
| Cohort A: Esophageal Squamous Cell Carcinoma (ESCC) | EXPERIMENTAL | Participants will receive Sacituzumab Govitecan-hziy (SG) 8 or 10 mg/kg on Days 1 and 8 of a 21-day cycle. Participants will continue treatment until disease progression or intolerable toxicity or consent withdrawal for any reason. |
| Cohort B: Gastric or Gastroesophageal Junction Adenocarcinoma (G/GEJC) | EXPERIMENTAL | Participants will receive SG 8 or 10 mg/kg on Days 1 and 8 of a 21-day cycle. Participants will continue treatment until disease progression or intolerable toxicity or consent withdrawal for any reason. |
| Cohort C: Cervical Cancer (CC) | EXPERIMENTAL | Participants will receive SG 10 mg/kg on Days 1 and 8 of a 21-day cycle. Participants will continue treatment until disease progression or intolerable toxicity or consent withdrawal for any reason. |
| Cohort D: Biliary Tract Cancer (BTC) | EXPERIMENTAL | Participants will receive SG 8 or 10 mg/kg on Days 1 and 8 of a 21-day cycle. Participants will continue treatment until disease progression or intolerable toxicity or consent withdrawal for any reason. |
| Cohort E: Lung Adenocarcinoma (LAC) | EXPERIMENTAL | Participants will receive SG 10 mg/kg on Days 1 and 8 of a 21-day cycle. Participants will continue treatment until disease progression or intolerable toxicity or consent withdrawal for any reason. |
| ERIBULIN WITH PAXMAN SCALP COOLING SYSTEM (PSCS) | EXPERIMENTAL | Participants will use Paxman Scalp Cooling System (PSCS) on days 1, 8 and 21 of each of their standard of care (SOC) treatment cycles with Eribulin. Study cyle is 21 days with total number of cycles based on discretion of treating provider up to 2 years. |
| ERIBULIN WITHOUT PAXMAN SCALP COOLING SYSTEM (PSCS) | ACTIVE_COMPARATOR | Participants will not use Paxman Scalp Cooling System (PSCS) during their standard of care (SOC) treatment with Eribulin. Study cyle is 21 days with total number of cycles based on discretion of treating provider up to 2 years. |
| SACITUZUMAB GOVITECAN WITH PAXMAN SCALP COOLING SYSTEM (PSCS) | EXPERIMENTAL | Participants will use Paxman Scalp Cooling System (PSCS) on days 1 and 21 of each of their standard of care (SOC) treatment cycles with SACITUZUMAB GOVITECAN. Study cyle is 21 days with total number of cycles based on discretion of treating provider up to 2 years. |
| SACITUZUMAB GOVITECAN WITHOUT PAXMAN SCALP COOLING SYSTEM (PSCS) | ACTIVE_COMPARATOR | Participants will not use Paxman Scalp Cooling System (PSCS) during their standard of care (SOC) treatment with SACITUZUMAB GOVITECAN. Study cyle is 21 days with total number of cycles based on discretion of treating provider up to 2 years. |
| TRASTUZUMAB DERUXTECAN WITH PAXMAN SCALP COOLING SYSTEM (PSCS) | EXPERIMENTAL | Participants will use Paxman Scalp Cooling System (PSCS) on days 1, 8 and 21 of each of their standard of care (SOC) treatment cycles with TRASTUZUMAB DERUXTECAN. Study cyle is 21 days with total number of cycles based on discretion of treating provider up to 2 years. |
| TRASTUZUMAB DERUXTECAN WITHOUT PAXMAN SCALP COOLING SYSTEM | ACTIVE_COMPARATOR | Participants will not use Paxman Scalp Cooling System (PSCS) during their standard of care (SOC) treatment with TRASTUZUMAB DERUXTECAN. Study cyle is 21 days with total number of cycles based on discretion of treating provider up to 2 years. |
| Sacituzumab Govitecan + Pembrolizumab | EXPERIMENTAL | The research study procedures include: screening for eligibility, research blood collections, at least two research biopsies, paired research stool collections, and study treatment including evaluations and follow up visits. Each Cycle =21 Days * Sacituzumab Govitecan (iv) fixed dose, administered twice per cycle * Pembrolizumab (iv) fixed dose administered once per cycle |
| Retreatment | EXPERIMENTAL | Participants who have attained a confirmed complete response (CR) who have been treated for at least 24 weeks on protocol therapy and had at least three cycles (with pembrolizumab and sacituzumab govitecan (Arm A) or sacituzumab govitecan alone (Arm B)) beyond the date when the initial CR was declared may be eligible for additional sacituzumab govitecan and/or pembrolizumab therapy if they progress after stopping study treatment. This retreatment is termed the Second Course Phase of this study and is only available if the study remains open and the subject meets protocol-specified conditions. |
| Cohort 1 Group 1: NSCLC [Adenocarcinoma + Squamous Cell Carcinoma (SCC)] | EXPERIMENTAL | Based on protocol amendment 1, participants with non-small cell lung cancer (NSCLC) subtypes such as adenocarcinoma and SCC with high trophoblast cell-surface antigen 2 (Trop-2) expression will receive sacituzumab govitecan-hziy (SG) 10 mg/kg of body weight, administered as a slow intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, unacceptable toxicity, study withdrawal, death, or another treatment discontinuation criteria will be met. |
| Cohort 1 Group 2: NSCLC (Adenocarcinoma) | EXPERIMENTAL | Based on protocol amendment 2 or 3, participants with NSCLC subtype of adenocarcinoma with or without high Trop-2 expression will receive SG 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, unacceptable toxicity, study withdrawal, death, or another treatment discontinuation criteria will be met. |
| Cohort 1 Group 3: NSCLC (SCC) | EXPERIMENTAL | Based on protocol amendment 2 or 3, participants with NSCLC subtype of SCC with or without high Trop-2 expression will receive SG 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, unacceptable toxicity, study withdrawal, death, or another treatment discontinuation criteria will be met. |
| Cohort 2: Head And Neck Squamous Cell Carcinoma (HNSCC) | EXPERIMENTAL | Participants with HNSCC will receive SG 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, unacceptable toxicity, study withdrawal, death, or another treatment discontinuation criteria will be met. |
| Cohort 3: Endometrial Cancer (EC) | EXPERIMENTAL | Participants with EC will receive SG 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, unacceptable toxicity, study withdrawal, death, or another treatment discontinuation criteria will be met. |
| Cohort 4: Extensive-Stage Small Cell Lung Cancer (ES-SCLC) | EXPERIMENTAL | Participants with ES-SCLC will receive SG 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, unacceptable toxicity, study withdrawal, death, or another treatment discontinuation criteria will be met. |
| CLOSED TO ENROLLMENT: Arm I (binimetinib, avelumab) | EXPERIMENTAL | Patients will receive a 15-day lead-in of binimetinib, followed by binimetinib PO BID and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| CLOSED TO ENROLLMENT: Arm II (anti-OX40 antibody PF-04518600, avelumab) | EXPERIMENTAL | Patients will receive a 15-day lead-in of anti-OX40 antibody PF-04518600, followed by anti-OX40 antibody PF-04518600 IV over 60 minutes and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| CLOSED TO ENROLLMENT: Arm III (utomilumab, avelumab) | EXPERIMENTAL | Patients will receive a 15-day lead-in of utomilumab, followed by utomilumab IV over 60 minutes every 4 weeks and avelumab IV over 60 minutes every 2 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm A (avelumab, binimetinib, liposomal doxorubicin) | EXPERIMENTAL | Patients receive a 15 day lead-in of binimetinib orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity. Patients then receive binimetinib PO BID on days 1-28, avelumab intravenously (IV) over 60 minutes on days 1 and 15, and liposomal doxorubicin IV over 60 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm B (avelumab, sacituzumab govitecan) | EXPERIMENTAL | Patients will receive a 15-day lead-in of sacituzumab govitecan given on day -15, followed by sacituzumab govitecan day 8 and day 15 of Cycle (C) 1; day 1,8, and 21 of C2; day 1, 15 and 21 of C3; day 8 and 15 of C4, and schedule continues with two weeks on, one week off for 21-day cycles. Patients also receive 10mg/kg avelumab over 60 minutes on day 1 and day 15 of each 28 day cycle. Cycles repeat in the absence of disease progression or unacceptable toxicity. |
| Arm C (avelumab, liposomal doxorubicin) | EXPERIMENTAL | Patients will receive a 15-day lead-in of liposomal doxorubicin, followed by liposomal doxorubicin on Day 1 and 10mg/kg avelumab over 60 minutes on Day 1 and Day 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Sacituzumab Govitecan Treatment | EXPERIMENTAL | Subjects enrolled in this study will receive Sacituzumab Govitecan in addition to their single agent Androgen Receptor Signaling Inhibitors (ARSI) as treatment for Castrate-Resistant Prostate Cancer. Dose will be calculated per protocol in milligrams based on the subject's body weight at the beginning of each cycle or more frequently if weight changes \>10%. Subjects will be treated on days 1 and 8 in a 21-day cycle, minimum 3 cycles. |
| Cohort 1: Sacituzumab Govitecan-hziy (SG) | EXPERIMENTAL | Participants with urothelial cancer (UC) previously treated with platinum-based and/or checkpoint inhibitors (CPIs) will receive SG 10 mg/kg intravenously (IV) on Days 1 and 8 of a 21-day cycle. |
| Cohort 2: SG | EXPERIMENTAL | Participants with UC who are ineligible for platinum-based therapy and failed therapy with previous immune CPI therapy will receive SG 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle. |
| Cohort 3: SG + Pembrolizumab | EXPERIMENTAL | Participants who have had progression or recurrence of UC following a platinum-containing regimen in the metastatic setting, or progression or recurrence of UC within 12 months of completion of platinum-based therapy as neoadjuvant or adjuvant therapy will receive SG 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle and pembrolizumab at the standard approved dose (200 mg) only on Day 1 of a 21-day cycle. Lower doses of SG may be tested based on dose-limiting toxicities (DLTs) observed to determine the Recommended Phase 2 Dose (RP2D) of SG in combination with pembrolizumab. |
| Cohort 4: SG + Cisplatin + Avelumab (Dose Escalation Phase) | EXPERIMENTAL | Participants with UC who have never received therapy with platinum in the metastatic setting or for unresectable locally advanced disease will first receive cisplatin (either at 70 mg/m\^2 on Day 1 of a 21-day cycle or at a split dose of 35 mg/m\^2 on Days 1 and 8 of a 21-day cycle with a maximum body surface area of 2) and sacituzumab govitecan-hziy with maximum dose of 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle for up to 6 cycles. Based on DLTs observed, two additional lower doses may be tested to determine RP2D of sacituzumab govitecan-hziy in combination with cisplatin. If premature termination of 1 agent occurs due to toxicity, the other agent may be continued to complete up to 6 cycles of therapy. For participants who have not progressed, maintenance therapy will begin with infusions of avelumab 800 mg every 2 weeks beginning on Cycle 1, Day 1 and every 2 weeks thereafter and sacituzumab govitecan-hziy 10 mg/kg on Days 1 and 8 every 21 days. |
| Cohort 4: SG + Cisplatin + Zimberelimab (ZIM) (Dose Expansion Phase) | EXPERIMENTAL | Participants with UC who have never received therapy with platinum in the metastatic setting or for unresectable locally advanced disease will first receive cisplatin (either at 70 mg/m\^2 on Day 1 of a 21-day cycle or at a split dose of 35 mg/m\^2 on Days 1 and 8 of a 21-day cycle with a maximum body surface area of 2) and sacituzumab govitecan-hziy with maximum dose of 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle for up to 6 cycles. If premature termination of 1 agent occurs due to toxicity, the other agent may be continued to complete up to 6 cycles of therapy. For participants who have not progressed, maintenance therapy will begin with infusions of sacituzumab govitecan-hziy 10 mg/kg on Days 1 and 8 every 21 days and zimberelimab 360 mg every 3 weeks (Day 1 of a 21-day cycle). |
| Cohort 5 (Arm 1): SG + ZIM | EXPERIMENTAL | Participants in Cohort 5 will have completed 4 to 6 cycles of gemcitabine (GEM) + cisplatin therapy without PD prior to study entry. The safety lead-in will be conducted, in 6 to 8 participants (treated with SG 10 mg/kg IV on Day 1 and Day 8 of a 21-day cycle + ZIM 360 mg IV every 3 weeks on a 21-day cycle). Upon completion of the safety lead-in, participants will receive SG 10 mg/kg IV on Days 1 and 8 of a 21-day cycle followed by ZIM 360 mg IV, every 3 weeks (Q3W) (Day 1 of a 21-day cycle) until PD, unacceptable toxicity, or loss of clinical benefit. participants who must discontinue 1 agent may continue the other until PD, unacceptable toxicity, or loss of clinical benefit. |
| Cohort 5 (Arm 2): Avelumab | EXPERIMENTAL | Participants in Cohort 5 will have completed 4 to 6 cycles of gemcitabine (GEM) + cisplatin therapy without PD prior to study entry. The safety lead-in will be conducted, in 6 to 8 participants (treated with SG 10 mg/kg IV on Day 1 and Day 8 of a 21-day cycle + ZIM 360 mg IV every 3 weeks on a 21-day cycle). Upon completion of the safety lead-in, participants will be randomized to receive avelumab 800 mg IV every 2 weeks (Q2W) until PD, unacceptable toxicity, or loss of clinical benefit. |
| Cohort 5 (Arm 3): ZIM | EXPERIMENTAL | Participants in Cohort 5 will have completed 4 to 6 cycles of gemcitabine (GEM) + cisplatin therapy without PD prior to study entry. The safety lead-in will be conducted, in 6 to 8 participants (treated with SG 10 mg/kg IV on Day 1 and Day 8 of a 21-day cycle + ZIM 360 mg IV every 3 weeks on a 21-day cycle). Upon completion of the safety lead-in, participants will be randomized to receive ZIM 360 mg IV Q3W (Day 1 of a 21-day cycle) until PD, unacceptable toxicity, or loss of clinical benefit. |
| Cohort 6 (Arm 1): SG | EXPERIMENTAL | Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and SG will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease. Treatment may be discontinued at any time, but participants will continue to be followed for tumor response until progression is documented, and alternate therapy is initiated. If participants discontinue therapy before evidence of radiologic progression, imaging should continue until radiologic progression is documented, if feasible. |
| Cohort 6 (Arm 2): SG + ZIM | EXPERIMENTAL | Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and SG in combination with ZIM will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease. The standard approved dose of SG will be used in combination with ZIM. Treatment may be discontinued at any time, but participants will continue to be followed for tumor response until progression is documented or alternate therapy is initiated. If participants discontinue therapy before evidence of radiologic progression, imaging should continue until radiologic progression is documented, if feasible. |
| Cohort 6 (Arm 3): SG + ZIM + Domvanalimab (DOM) | EXPERIMENTAL | Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and SG in combination with ZIM and DOM will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease. |
| Cohort 6 (Arm 4): Carboplatin (CARBO) + Gemcitabine (GEM) | EXPERIMENTAL | Upon completion of the safety lead-in, participants in Cohort 6 will be randomized and CARBO in combination with GEM will be administered in cisplatin-ineligible participants who have never received therapy in the metastatic setting or for unresectable locally advanced disease. Participants without disease progression as assessed by the investigator after completion of 4 to 6 cycles of therapy may continue with maintenance therapy (avelumab 800 mg every 2 weeks) until loss of clinical benefit. |
| Cohort 7 (Phase 1: Safety Lad-in and Dose Expansion): SG + Enfortumab Vedotin (EV) + ZIM | EXPERIMENTAL | In the safety lead-in phase, participants will receive a starting dose level of SG 7.5 mg/kg IV and starting dose level of EV 1.25 mg/kg IV will be administered on Days 1 and 8 of each 21-day cycle and ZIM 360 mg IV will be administered on Day 1 of each 21-day cycle. In dose-expansion, participants will receive SG IV and EV IV at the RP2Ds on Days 1 and 8 of each 21-day cycle and ZIM 360 mg IV on Day 1 of each 21-day cycle. |
| Cohort 7 (Phase 2: Arm 1): SG + EV + ZIM | EXPERIMENTAL | Upon completion of the Cohort 7 dose-expansion phase, participants will receive SG IV at the RP2D in combination with EV IV at the RP2D, and ZIM 360 mg IV until PD, unacceptable toxicity, or loss of clinical benefit. |
| Cohort 7 (Phase 2: Arm 2): EV + ZIM | EXPERIMENTAL | Upon completion of the Cohort 7 dose-expansion phase, participants will receive EV 1.25 mg/kg IV and ZIM 360 mg IV. |
| Cohort 7 (Phase 2: Arm 3): Optional Dose Optimization SG + EV + ZIM | EXPERIMENTAL | Upon completion of the Cohort 7 dose-expansion phase, participants will receive SG IV at 1 dose level below the RP2D in combination with EV 1.25 mg/kg IV and ZIM 360 mg IV. |
| Dose Escalation Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) | EXPERIMENTAL | Participants will be given the study drugs Enfortumab Vedotin and then Sacituzumab Govitecan on Days 1 and 8 of a 21-day study cycle. Dose escalation and de-escalation for the Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) combination will be guided using the Bayesian optimal interval (BOIN) design with up to 4 dose level escalations. |
| Dose Expansion Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) | EXPERIMENTAL | Participants will be given the study drugs Enfortumab Vedotin and then Sacituzumab Govitecan on Days 1 and 8 of each 21-day study cycle. Three dose levels of this drug combination will be studied with 3-18 patients per dose level depending on treatment-related dose limiting toxicities. |
| Sacituzumab Govitecan (SG) and Enfortumab vedotin-ejfv (EV) and Pembrolizumab | EXPERIMENTAL | Participants will be given a triplet regimen of Enfortumab Vedotin 1.25mg/kg, Sacituzumab Govitecan 7.5mg/kg (D1 and D8 every three weeks), and Pembrolizumab 200mg (D1 every 3 weeks) or 400 mg (D1 every 6 weeks) as a front-line therapy. Dose reductions of Enfortumab Vedotin to 1, 0.75 and 0.5 mg/kg will be permitted while Sacituzumab Govitecan can be dose reduced to 5 mg/kg. No dose reductions of Pembrolizumab are permitted. Following C1D1, drugs may be held independently per investigator discretion. A safety run-in will be conducted for the first 12 patients to evaluate the tolerability of the triplet regimen using Bayesian toxicity monitoring (BTOX). The first stage will enroll 6 patients, and if there are 2 or fewer DLTs, then next 6 patients will be enrolled. The study will be halted if there are 5 or more DLTs observed among the total of 12 evaluable patients. |
| Phase 1 | EXPERIMENTAL | Participants will receive SG until progressive disease (PD), death, unacceptable toxicity, or another treatment discontinuation criterion is met. |
| Phase 2: Expansion | EXPERIMENTAL | Participants will receive SG until PD, death, unacceptable toxicity, or another treatment discontinuation criterion is met. |
| Debio 0123 + Sacituzumab govitecan | EXPERIMENTAL | Phase Ib of the study will adopt the Bayesian Logistic Regression Model (BLRM) with Overdosing Control. Patients with TNBC and HR+/HER2- advanced/metastatic breast cancer will receive multiple doses of Debio 0123 administered orally during 6 days of each 21-day cycle and 10 mg/kg of Sacituzumab govitecan administered intravenously on D1 and D8 of each 21-day cycle in order to find the RP2D for Debio 0123 when administered in combination with Sacituzumab govitecan. In phase II study, patients with TNBC or HR+/HER2- advanced/metastatic breast cancer will receive the RP2D of Debio 0123 administered orally during 6 days of each 21-day cycle in combination with 10 mg/kg of Sacituzumab govitecan administered intravenously on D1 and D8 of each 21-day cycle until documented disease progression, death, unacceptable toxicity, or discontinuation from the study treatment for any other reason, whichever occurs first. |
| SG + Adaptive radiotherapy | EXPERIMENTAL | Sacituzumab Govitecan, IV, 8 mg/kg, 21-day cycles for 1 loading cycle prior to radiation and two subsequent cycles with concurrent adaptive radiotherapy |
| Sacituzumab Govitecan-hziy 6 mg, Advanced Solid Tumors | EXPERIMENTAL | (Phase 1 Cohort A: dose escalation) Japanese participants with advanced solid tumors will receive sacituzumab govitecan-hziy (SG) 6 mg/kg by intravenous (IV) injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. |
| Sacituzumab Govitecan-hziy 8 mg, Advanced Solid Tumors | EXPERIMENTAL | (Phase 1 Cohort A: dose escalation) Japanese participants with advanced solid tumors will receive SG 8 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. |
| Sacituzumab Govitecan-hziy 10 mg, Advanced Solid Tumors | EXPERIMENTAL | (Phase 1 Cohort A: dose escalation) Japanese participants with advanced solid tumors will receive SG 10 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. |
| Sacituzumab Govitecan-hziy 6 mg, UGT1A1 Polymorphism | EXPERIMENTAL | (Phase 1 Cohort B: dose escalation) Japanese participants with UGT1A1 polymorphism will receive SG 6 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. |
| Sacituzumab Govitecan-hziy 10 mg, UGT1A1 Polymorphism | EXPERIMENTAL | (Phase 1 Cohort B: dose escalation) Japanese participants with UGT1A1 polymorphism will receive SG 10 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. |
| Sacituzumab Govitecan-hziy, Metastatic Triple-negative Breast Cancer (mTNBC) | EXPERIMENTAL | (Phase 2: dose expansion) Japanese participants with mTNBC will receive SG at the recommended Phase 2 dose (RP2D) on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. |
| Sacituzumab Govitecan-hziy, HR+/HER2- Metastatic Breast Cancer (HR+/HER2- mBC) | EXPERIMENTAL | (Phase 2) Japanese participants with HR+/HER2- mBC will receive SG at the recommended Phase 2 dose (RP2D) on Day 1 and Day 8 of a 21 day cycle until disease progression or unacceptable toxicity. |
| Sacituzumab Govitecan-hziy, Metastatic Urothelial Carcinoma (mUC) | EXPERIMENTAL | (Phase 2) Japanese participants with mUC will receive SG at the recommended Phase 2 dose (RP2D) on Day 1 and Day 8 of a 21 day cycle until disease progression or unacceptable toxicity. |
| Advanced or Metastatic Solid Tumor and Moderate Liver Impairment | EXPERIMENTAL | Participants with advanced solid tumor and moderate hepatic impairment will receive an escalating dose of sacituzumab govitecan-hziy on Days 1 and 8. The dose-escalation plan will start at 5 mg/kg and escalate to 7.5 mg/kg, and finally 10 mg/kg, if deemed to be safe. At the completion of study treatment, participants who are deriving benefit from sacituzumab govitecan-hziy may continue to receive treatment in a Gilead sponsored rollover study (IMMU-132-14; NCT04319198). |
| Advanced or Metastatic Solid Tumor and Normal Liver function | EXPERIMENTAL | Participants with advanced or metastatic solid tumor and normal hepatic function will receive sacituzumab govitecan-hziy 10 mg/kg on Days 1 and 8. At the completion of study treatment, participants who are deriving benefit from sacituzumab govitecan-hziy may continue to receive treatment in a Gilead sponsored rollover study (IMMU-132-14; NCT04319198). |
| Atezolizumab + Nab-Paclitaxel | ACTIVE_COMPARATOR | 1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus nab-paclitaxel until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed. |
| Atezolizumab + Nab-Paclitaxel + Tocilizumab | EXPERIMENTAL | 1L PD-L1-positive participants will receive combination treatment with atezolizumab plus nab-paclitaxel and tocilizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed and participant follow-up is complete. |
| Atezolizumab + Sacituzumab Govitecan | EXPERIMENTAL | 1L PD-L1-positive participants will receive doublet combination treatment with atezolizumab plus sacituzumab govitecan until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed. |
| Capecitabine | ACTIVE_COMPARATOR | 2L CIT-naïve participants will receive capecitabine until unacceptable toxicity or disease progression per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). Participants who progressed on treatment may have the option of receiving atezolizumab along with chemotherapy (chemo) during stage 2, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete. |
| Atezolizumab + Ipatasertib | EXPERIMENTAL | 2L CIT-naïve participants will receive doublet combination treatment with atezolizumab plus ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete. |
| Atezolizumab + SGN-LIV1A | EXPERIMENTAL | 2L CIT-naïve participants will receive doublet combination treatment with atezolizumab plus SGNLIV1A until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Patients who experience loss of clinical benefit as determined by the investigator or unacceptable toxicity related to SGN-LIV1A will be given the option of receiving Atezolizumab + chemo during Stage 2, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete. |
| Atezolizumab + Selicrelumab + Bevacizumab | EXPERIMENTAL | 2L-CIT-naïve participants will receive doublet combination treatment with atezolizumab plus selicrelumab and bevacizumab until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Participants who progressed on treatment may have the option of receiving atezolizumab + chemo, provided they meet the eligibility criteria. Enrollment is closed and participant follow-up is complete. |
| Atezolizumab + Chemo (Gemcitabine + Carboplatin or Eribulin) | EXPERIMENTAL | 2L CIT-naïve participants enrolled in the active comparator arm who experience disease progression per RECIST v1.1 and 2L CIT-naïve participants enrolled in an experimental arm who experience loss of clinical benefit as determined by the investigator may receive doublet combination treatment with atezolizumab plus chemo (gemcitabine + carboplatin or eribulin) until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Enrollment is closed and participant follow-up is complete. |
| Inavolisib (Dose #2) + Abemaciclib + Fulvestrant | EXPERIMENTAL | HR+ participants will receive treatment with inavolisib plus abemaciclib plus fulvestrant until unacceptable toxicity or disease progression determined by the investigator according to RECIST v1.1. |
| Inavolisib (Dose #2) + Ribociclib (Dose #1) + Fulvestrant | EXPERIMENTAL | HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Inavolisib (Dose #2) + Ribociclib (Dose #1) + Letrozole | EXPERIMENTAL | HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Inavolisib (Dose #2) + Ribociclib (Dose #2) + Fulvestrant | EXPERIMENTAL | HR+ participants will receive treatment with inavolisib plus ribociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Inavolisib (Dose #2) + Ribociclib (Dose #2) + Letrozole | EXPERIMENTAL | HR+ participants will receive treatment with inavolisib plus ribociclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Inavolisib (Dose #2) + Abemaciclib + Letrozole | EXPERIMENTAL | HR+ participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Inavolisib (Dose #1) + Trastuzumab Deruxtecan | EXPERIMENTAL | HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. Enrollment is closed. |
| Inavolisib (Dose #2) + Trastuzumab Deruxtecan | EXPERIMENTAL | HER2+/HER2-low participants will receive inavolisib + trastuzumab deruxtecan until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. Enrollment is closed. |
| Empagliflozin + Inavolisib (Dose #2) + Fulvestrant ± Palbociclib | EXPERIMENTAL | Participants with locally advanced or metastatic, HR+, HER2- participants will receive empagliflozin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Metformin + Inavolisib (Dose #2) + Fulvestrant ± Palbociclib | EXPERIMENTAL | Participants with locally advanced or metastatic, HR+, HER2- participants will receive metformin plus inavolisib plus fulvestrant with or without palbociclib until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Inavolisib (Dose #2) + Atirmociclib (Atirmo) + Fulvestrant | EXPERIMENTAL | Participants will receive inavolisib plus atirmociclib plus fulvestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Inavolisib (Dose #1) + Abemaciclib + Letrozole | EXPERIMENTAL | HR+ participants will receive treatment with inavolisib plus abemaciclib plus letrozole until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Inavolisib (Dose #1) + Abemaciclib + Giredestrant | EXPERIMENTAL | HR+ participants will receive treatment with inavolisib plus abemaciclib plus giredestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Inavolisib (Dose #2) + Abemaciclib + Giredestrant | EXPERIMENTAL | HR+ participants will receive treatment with inavolisib plus abemaciclib plus giredestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Inavolisib (Dose #2) + Ribociclib (Dose #1) + Giredestrant | EXPERIMENTAL | HR+ participants will receive treatment with inavolisib plus ribociclib plus giredestrant until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1. |
| Sacituzumab Govitecan-hziy (SG) 8 mg/kg | EXPERIMENTAL | Participants will receive sacituzumab govitecan-hziy (SG) 8 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity. |
| SG 10 mg/kg | EXPERIMENTAL | Participants will receive SG 10 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity. |
| SG 12 mg/kg | EXPERIMENTAL | Participants will receive SG 12 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity. |
| SG 18 mg/kg | EXPERIMENTAL | Participants will receive SG 18 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity. |
| Breast Brain Metastasis and Glioblastoma | EXPERIMENTAL | Sacituzumab Govitecan treatment will be initiated with a 10mg/kg standard dose without any dose escalation on day-1, prior to surgery. Sacituzumab govitecan and will continue to be administered by IV infusion over 3 hours on Days 1 and 8 of a 21 day cycle post-operatively until progression. |
| Name | Type | Description |
|---|---|---|
| Sacituzumab govitecan | DRUG | 10 mg/kg twice on Days 1 and 8 of a continuous 21-day treatment cycle |
| Pembrolizumab | DRUG | 200 mg every 3 weeks (q3w) |
| Pembrolizumab 25 mg/1 ML Intravenous Solution [KEYTRUDA] | DRUG | Pembrolizumab 200 mg will be administered as a 30-minute i.v. infusion every 3 weeks. |
| SoC Chemotherapy | DRUG | Standard of care chemotherapy as per common treatment guidelines and recommendations |
| Sacituzumab Govitecan (SG) | DRUG | Administered intravenously |
| Topotecan | DRUG | Administered intravenously |
| Amrubicin (Japan only) | DRUG | Administered intravenously |
| Lurbinectedin (regions/countries where approved and available) | DRUG | Administered intravenously |
| Sacituzumab govitecan-hziy | DRUG | Administered intravenously |
| Doxorubicin | DRUG | Administered intravenously |
| Paclitaxel | DRUG | Administered intravenously |
| Nab-paclitaxel | DRUG | Administered intravenously |
| Capecitabine | DRUG | Administered orally |
| Sacituzumab govitecan-hziy (SG) | DRUG | Administered intravenously |
| Gemcitabine | DRUG | Administered intravenously |
| Carboplatin | DRUG | Administered intravenously |
| Docetaxel | DRUG | Administered intravenously |
| Vinflunine | DRUG | Administered intravenously |
| Eribulin Mesylate Injection | DRUG | Eribulin is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts. |
| Capecitabine Oral Product | DRUG | Capecitabine is administered orally (PO) following recommended doses and regimens as per approved package inserts. |
| Gemcitabine Injection | DRUG | Gemcitabine is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts. |
| Vinorelbine injection | DRUG | Vinorelbine is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts. |
| Cisplatin | DRUG | 25mg/m3 weekly or 75 mg/m3 q3w |
| Eribulin | DRUG | Administered intravenously per NCCN guidelines |
| Vinorelbine | DRUG | Administered intravenously per NCCN guidelines |
| Trastuzumab | DRUG | Humanized IgG1 kappa monoclonal antibody, 150mg single-dose vial, via intravenous infusion per protocol. |
| Trastuzumab and Hyaluronidase-oysk | DRUG | Recombinant monoclonal antibody, 6 mL vial, via subcutaneous injection per protocol. |
| Atezolizumab | DRUG | Atezolizumab 1200mg via IV infusion on Day 1 of a 21-day cycle (ie, once every 3 weeks) |
| Durvalumab | DRUG | Durvalumab 1500mg via IV infusion on Day 1 of a 21-day cycle (ie, once every 3 weeks) |
| Loperamide | DRUG | Loperamide : 2 mg orally (PO), twice a day (BID), or 4 mg once a day (QD) during three consecutive days after administration of sacituzumab govitecan, (D2, D3, D4 and D9, D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician). |
| Granulocyte Colony-Stimulating Factor | DRUG | G-CSF : 30 MU subcutaneously (SC) QD during two consecutive days, 48 hours after administration of sacituzumab govitecan (D3, D4 and D10, D11) during the first two cycles (consider extending to the next cycle at the discretion of the physician). |
| Sacituzumab Govitecan + Zimberelimab | DRUG | Sacituzumab Govitecan 7.5 mg/kg IV for 3 cycles Zimberelimab 360 mg IV for 16 cycles Patients will be treated with Sacituzumab Govitecan 1,8q21 plus + Zimberelimab q21 for 3 cycles then radiological imaging and TURB will be repeated and patients with Stability of disease or down staging will continue Zimberelimab until disease progression, or unacceptable toxicities or completion of treatment (16 cycles). Patients with progressive disease after 3 cycles of study intervention will be treated as per clinical practice. |
| Nivolumab | DRUG | Given IV |
| Paxman Scalp Cooling System | DEVICE | Cap attached to coolant lines connected to a refrigeration unit placed on scalp |
| Trastuzumab deruxtecan | DRUG | Intravenous Infusion |
| Anti-OX40 Antibody PF-04518600 | BIOLOGICAL | Given IV |
| Avelumab | DRUG | Given IV |
| Binimetinib | DRUG | Given PO |
| Utomilumab | BIOLOGICAL | Given IV |
| Liposomal Doxorubicin | DRUG | Given IV |
| Zimberelimab | DRUG | Administered intravenously |
| Domvanalimab | DRUG | Administered intravenously |
| Enfortumab Vedotin | DRUG | Administered intravenously |
| Enfortumab vedotin-ejfv (EV) | DRUG | Intravenous infusion |
| Debio 0123 and Sacituzumab govitecan | DRUG | Debio 0123 will be administered orally during 6 days of each 21-day cycle in combination with 10 mg/kg of Sacituzumab govitecan administered intravenously on D1 and D8 of each 21-day cycle until documented disease progression, death, unacceptable toxicity, or discontinuation from the study treatment for any other reason, whichever occurs first. |
| Adaptive Radiotherapy | RADIATION | Concurrently, participants will receive an individualized tailored plan for radiation therapy. |
| Ipatasertib | DRUG | Ipatasertib will be administered by mouth 400 mg once a day, on Days 1-21 of each 28-day cycle. |
| SGN-LIV1A | DRUG | SGN-LIV1A will be administered IV, 2.5 milligrams per kilogram (mg/kg) (maximum calculated dose 250 mg), on Day 1 of each 21-day cycle. |
| Bevacizumab | DRUG | Bevacizumab will be administered IV, 10 mg/kg, on Days 1 and 15 of each 28-day cycle. |
| Chemotherapy (Gemcitabine + Carboplatin or Eribulin) | DRUG | Gemcitabine will be administered by IV, 1000 mg/m\^2, along with carboplatin, by IV, on Days 1 and 8 of each 21-day cycle. Or Eribulin will be administered IV, 1.4 mg/m\^2 on Days 1 and 8 of each 21-day cycle. |
| Selicrelumab | DRUG | Selicrelumab will be administered by subcutaneous (SC) injection, at a fixed dose of 16 mg on Day 1 of Cycles 1 to 4 and every third cycle thereafter (Cycle = 28 days). |
| Tocilizumab | DRUG | Tocilizumab will be administered IV, 8 mg/kg on Day 1 of each 28-day cycle. |
| Abemaciclib | DRUG | Abemaciclib tablets will be administered at a dose of 150 mg twice daily by mouth on Days 1-28 of each 28-day cycle. |
| Fulvestrant | DRUG | For Inavolisib + Abemaciclib + Fulvestrant, Inavolisib + Ribociclib (Dose #1) + Fulvestrant, Inavolisib + Ribociclib (Dose #2) + Fulvestrant, or Inavolisib + Atirmociclib + Fulvestrant arms: Fulvestrant 500 mg, administered as an IM injection on Days 1 and 15 of Cycle 1, followed by Day 1 of each 28-day cycle thereafter. For Empa + Inavolisib + Fulvestrant ± Palbociclib, or Metformin + Inavolisib + Fulvestrant ± Palbociclib arms: Fulvestrant 500 mg, administered as an IM injection on Day 1 and as per local prescribing guidelines thereafter. |
| Ribociclib (Dose #1) | DRUG | Ribociclib tablets will be administered by mouth once daily. |
| Inavolisib (Dose #1) | DRUG | Inavolisib tablets will be administered by mouth once daily. |
| Ribociclib (Dose #2) | DRUG | Ribociclib tablets will be administered by mouth once daily. |
| Letrozole | DRUG | Letrozole tablets will be administered at a dose of 2.5 mg once a day by mouth on Days 1-28 of each 28-day cycle. |
| Inavolisib (Dose #2) | DRUG | Inavolisib tablets will be administered by mouth OD. |
| Empagliflozin | DRUG | Empagliflozin, administered orally, once daily (QD) |
| Palbociclib | DRUG | For Empagliflozin + Inavolisib + Fulvestrant ± Palbociclib arm: Palbociclib 125 mg administered orally, QD in Cycle 1 followed by 125 mg on Days 1-21 of each cycle. For Metformin + Inavolisib + Fulvestrant ± Palbociclib arm: Palbociclib 125 mg administered orally, QD in Cycle 1, followed by 125 mg on Days 1-21 of each cycle (Cycle=28 days). |
| Metformin | DRUG | Metf 1000 mg administered orally QD. |
| Atirmociclib | DRUG | Atirmociclib administered orally, BID on Days 1-28 for each 28-day cycle. |
| Giredestrant | DRUG | Giredestrant 30 mg will be administered by mouth once daily, on Days 1-28 of each 28-day cycle. |
Inclusion Criteria: 1. ER + PR negative or low positive (≤10% positive cells in IHC), and HER2 negative (i.e., IHC 0 - 1+ or IHC 2+ with FISH negative) breast cancer 2. All patients, independent from gender 3. ≥18 years at diagnosis 4. Histologically confirmed unilateral, primary invasive carcinoma...
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Sacituzumab govitecan is an antibody-drug conjugate developed by Gilead Sciences for the treatment of several cancers. It is being studied in advanced breast cancer, triple-negative breast cancer, bladder cancer, cervical cancer, small cell lung cancer, and advanced solid tumors. It is an investigational therapy in clinical development.
Sacituzumab govitecan is being studied for advanced breast cancer, triple-negative breast cancer, bladder cancer, cervical cancer, extensive-stage small cell lung cancer, and advanced or metastatic solid tumors. These are the cancer types under investigation in its clinical program, which includes both early-phase and late-phase studies.
Sacituzumab govitecan is developed by Gilead Sciences, Inc., which trades on the Nasdaq under the ticker GILD. Gilead is the sponsor of the clinical trials evaluating the drug across breast cancer, lung cancer, and other solid tumor types.
Sacituzumab govitecan is in clinical development and is not approved based on the studies described here. Its program spans Phase 1, Phase 2, and Phase 3 trials. Seven trials are listed in total, with four currently active and one completed, enrolling 3,174 participants overall.
Sacituzumab govitecan trials include NCT07339059, a Phase 2 maintenance study with atezolizumab or durvalumab in extensive-stage small cell lung cancer, and NCT07178730, a Phase 3 neoadjuvant study with pembrolizumab in triple-negative early breast cancer. NCT06926920 is a Phase 1 alternative dose and schedule study in advanced triple-negative breast cancer, and NCT06801834 is a Phase 3 study versus standard of care in previously treated extensive-stage small cell lung cancer.
Yes. Sacituzumab govitecan-hziy is the same drug as sacituzumab govitecan. Other names used for it include SG, Debio 0123, and sacituzumab govitecan plus zimberelimab, which refers to a combination regimen pairing the drug with zimberelimab. Searches for any of these names refer to the same Gilead Sciences asset.