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Sacituzumab Govitecan-hziy

Phase 3

Non-small Cell Lung Cancer | Small molecule | Oncology |Gilead Sciences, Inc.|Last Updated: Jul 15, 2026

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Trial Design
RandomizedCONTROLLEDDMC
Total Trials2
Total Enrollment796
FDA Designations
No designations recorded
Clinical trial landscape

Sacituzumab Govitecan-hziy · 19 trials · 32 indications

Phase 3 9Phase 2 6Phase 1 4
NCT06486441Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Participants With Endometrial Cancer After Platinum-Based Chemotherapy and Immunotherapy (ASCENT-GYN-01/GOG-3104/ENGOT-en26)Endometrial Cancer
ACTIVE NOT_RECRUITING640 Analytics
NCT05840211Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Patients With Hormone Receptor-positive/Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Metastatic Breast Cancer Who Have Received Endocrine TherapyLocally Advanced or Unresectable Metastatic Breast Cancer
ACTIVE NOT_RECRUITING654 Analytics
NCT05633654Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy (ASCENT-05/AFT-65 OptimICE-RD/GBG 119/NSABP B-63)Triple Negative Breast Cancer
RECRUITING1,514 Analytics
NCT05382286Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast CancerTriple Negative Breast Cancer
ACTIVE NOT_RECRUITING443 Analytics
NCT05382299Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Patients With Previously Untreated Locally Advanced Inoperable or Metastatic Triple-Negative Breast CancerTriple Negative Breast Cancer
ACTIVE NOT_RECRUITING623 Analytics
NCT05089734Study of Sacituzumab Govitecan (SG) Versus Docetaxel in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)Non-Small Cell Lung Cancer
ACTIVE NOT_RECRUITING603 Analytics
NCT04527991Study of Sacituzumab Govitecan Versus Physician's Choice of Treatment in Participants With Urothelial Cancer That Cannot Be Removed or Has SpreadLocally Advanced or Metastatic Unresectable Urothelial Cancer
COMPLETED711 Analytics
NCT04639986Asian Study of Sacituzumab Govitecan (IMMU-132) in HR+/HER2- Metastatic Breast Cancer (MBC)Metastatic Breast Cancer
ACTIVE NOT_RECRUITING331 Analytics
NCT03901339Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Participants With HR+/HER2- Metastatic Breast CancerMetastatic Breast Cancer
COMPLETED543 Analytics
PHASE3ACTIVE NOT_RECRUITING
Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Participants With Endometrial Cancer After Platinum-Based Chemotherapy and Immunotherapy (ASCENT-GYN-01/GOG-3104/ENGOT-en26)
Endometrial CancerUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Patients With Hormone Receptor-positive/Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Metastatic Breast Cancer Who Have Received Endocrine Therapy
Locally Advanced or Unresectable Metastatic Breast CancerUnlock trial analytics
PHASE3RECRUITING
Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice in Patients With Triple Negative Breast Cancer Who Have Residual Invasive Disease After Surgery and Neoadjuvant Therapy (ASCENT-05/AFT-65 OptimICE-RD/GBG 119/NSABP B-63)
Triple Negative Breast CancerUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Study of Sacituzumab Govitecan-hziy and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer
Triple Negative Breast CancerUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Patients With Previously Untreated Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer
Triple Negative Breast CancerUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Study of Sacituzumab Govitecan (SG) Versus Docetaxel in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
Non-Small Cell Lung CancerUnlock trial analytics
PHASE3COMPLETED
Study of Sacituzumab Govitecan Versus Physician's Choice of Treatment in Participants With Urothelial Cancer That Cannot Be Removed or Has Spread
Locally Advanced or Metastatic Unresectable Urothelial CancerUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
Asian Study of Sacituzumab Govitecan (IMMU-132) in HR+/HER2- Metastatic Breast Cancer (MBC)
Metastatic Breast CancerUnlock trial analytics
PHASE3COMPLETED
Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Participants With HR+/HER2- Metastatic Breast Cancer
Metastatic Breast CancerUnlock trial analytics
Study Endpoints
Primary Endpoints
Progression-Free Survival (PFS) As Assessed by Blinded Independent Central Review (BICR)
Up to approximately 27 months

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.

Overall Survival (OS)
Up to approximately 47 months

Overall survival (OS) is defined as time from the date of randomization until death due to any cause.

Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Up to approximately 29 months

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.

Invasive Disease-free Survival (iDFS)
Up to 60 months

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.

Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Randomization up to approximately 33 months

PFS is defined as the time from the date of randomization until the date of objective progressive disease (PD) or death (whichever comes first).

Progression-free Survival (PFS)
Up to 4 years

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).

Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) Assessment
Up to 42.8 months

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.

Overall Response Rate (ORR)
1 year

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.

Objective Response Rate as Assessed by Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Up to 22 Months
Percentage of Participants Experiencing Dose-limiting Toxicities (DLTs) per Dose Level in the Safety Run-in Cohorts
First dose date up to 21 days
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) By Investigator Assessment
Up to 4 years

ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR).

Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) By Independent Review Committee (IRC)
Up to 3 years

ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR).

Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator's Assessment
Cohort 1: Up to 5.3 years; Cohort 2: Up to 3.4 years; Cohort 3: Up to 3.3 years; Cohort 4: Up to 2.5 years

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.

Overall Response Rate (ORR) Based on Central Review by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Criteria (Cohorts 1 to 4 and 6)
Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))

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.

Progression free survival (PFS) Based on Central Review by RECIST 1.1 criteria (Cohort 5)
Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))

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 Based on Investigator Review by RECIST 1.1 Criteria (Cohort 7)
Up to Survival Follow-up Visit (maximum of 2 years after Safety Follow-up Visit (30 days after last dose date))

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.

Percentage of Participants Experiencing Treatment Emergent Adverse Events (TEAEs) (Cohort 7)
First dose date up to last dose date plus 30 days (approximately 3 years)
Percentage of Participants Experiencing any Clinically Significant Laboratory Abnormalities (Cohort 7)
First dose date up to last dose date plus 30 days (approximately 3 years)
Phase 1: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs)
First dose up to 28 days
Phase 1 and 2: Percentages of Participants Experiencing Adverse Events (AEs)
First dose up to 30 days post last dose (Up to 3 years)
Phases 1 and 2: Percentages of Participants Experiencing Laboratory Abnormalities
First dose up to 30 days post last dose (Up to 3 years).
Phases 1 and 2: Percentages of Participants Experiencing AEs Leading to Dose Reductions, Dose Interruptions, and Treatment Discontinuations
First dose up to 30 days post last dose (Up to 3 years).
Phases 1 and 2: Objective Response Rate (ORR)
Up to 9 months

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.

Phase 2: Progression-Free Survival (PFS)
Up to 9 months

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.

Phase 1: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) Defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03
First dose date to last dose date (Up to 15 weeks) plus 30 days
Phase 1: Percentage of Participants Experiencing Laboratory Abnormalities Defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03
First dose date to last dose date (Up to 15 weeks) plus 30 days
Phase 1: Percentage of Participants Experiencing Dose-limiting toxicity (DLTs) per Dose level
First dose date up to 21 days
Phase 2:(Metastatic Triple-negative Breast Cancer (mTNBC);Hormone Receptor-positive/Human Epidermal Growth Factor Receptor 2-negative Metastatic Breast Cancer (HR+/HER2- mBC) Cohorts):Objective Response Rate (ORR) as Assessed by IRC
Up to 17 months

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).

Phase 2 (Metastatic Urothelial Cancer (mUC) Cohort): ORR as Assessed by Investigator
Up to 17 months

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)

Percentage of Participants experiencing Treatment Emergent Adverse Events (TEAEs) and Serious AEs
First dose date up to Day 38
Percentage of Participants Experiencing Any Dose Limiting Toxicities (DLTs)
Up to Day 22 (for participants receiving SG on Day 1); Up to Day 28 (for participants receiving SG on Day 8)
Percentage of Participants Experiencing Any Clinically Significant Laboratory Abnormalities
First dose date up to Day 38
Pharmacokinetic (PK) Parameter: Cmax of Free SN-38 and Sacituzumab Govitecan-hziy
Days 1 and 8

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.

PK Parameter: AUC 0-168 of Free SN-38 and Sacituzumab Govitecan-hziy
Days 1 and 8

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.

Percentage of Participants who Develop Anti-Sacituzumab Govitecan-hziy Antibodies
Day 1 (Predose) and Day 22
Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events
First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months) plus 30 days

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.

Percentage of Participants Who Permanently Discontinued Sacituzumab Govitecan-hziy (SG) Due to Any Adverse Events, Excluding Adverse Events Leading to Death
First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)

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).

Percentage of Participants Who Required Dose Interruption Due to Any Adverse Events
First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)

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).

Objective Response Rate (ORR) by Independent Central Review (ICR)
Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

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.

Objective Response Rate by Local Assessment
Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

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.

Secondary Endpoints
Objective Response Rate (ORR) as Assessed by BICR
Up to approximately 47 months
Change from Baseline in the Physical Functioning Domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Version 3.0 (EORTC QLQ-C30) at Week 16
Baseline, Week 16
PFS as Assessed by Investigator
Up to approximately 27 months
Unlock Study Endpoints
Study Design & Arms
AllocationRANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Sacituzumab Govitecan (SG)EXPERIMENTALParticipants 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_COMPARATORParticipants 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)EXPERIMENTALParticipants 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) + PembrolizumabEXPERIMENTALParticipants 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 + CapecitabineACTIVE_COMPARATORParticipants 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_COMPARATORParticipants 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
DocetaxelACTIVE_COMPARATORParticipants 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 ChoiceACTIVE_COMPARATORParticipants 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-hziyEXPERIMENTALParticipants will receive Sacituzumab Govitecan-hziy 10 mg/kg on Days 1 and 8 of a 21-day cycle.
SacituzumabEXPERIMENTAL -
Sacituzumab Govitecan-hziy (SG) + Pembrolizumab (Cohort A)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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-inEXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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 1 Group 1: NSCLC [Adenocarcinoma + Squamous Cell Carcinoma (SCC)]EXPERIMENTALBased 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)EXPERIMENTALBased 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)EXPERIMENTALBased 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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.
Cohort 1: Sacituzumab Govitecan-hziy (SG)EXPERIMENTALParticipants 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: SGEXPERIMENTALParticipants 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 + PembrolizumabEXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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)EXPERIMENTALParticipants 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 + ZIMEXPERIMENTALParticipants 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): AvelumabEXPERIMENTALParticipants 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): ZIMEXPERIMENTALParticipants 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): SGEXPERIMENTALUpon 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 + ZIMEXPERIMENTALUpon 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)EXPERIMENTALUpon 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)EXPERIMENTALUpon 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) + ZIMEXPERIMENTALIn 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 + ZIMEXPERIMENTALUpon 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 + ZIMEXPERIMENTALUpon 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 + ZIMEXPERIMENTALUpon 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.
Phase 1EXPERIMENTALParticipants will receive SG until progressive disease (PD), death, unacceptable toxicity, or another treatment discontinuation criterion is met.
Phase 2: ExpansionEXPERIMENTALParticipants will receive SG until PD, death, unacceptable toxicity, or another treatment discontinuation criterion is met.
Sacituzumab Govitecan-hziy 6 mg, Advanced Solid TumorsEXPERIMENTAL(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 TumorsEXPERIMENTAL(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 TumorsEXPERIMENTAL(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 PolymorphismEXPERIMENTAL(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 PolymorphismEXPERIMENTAL(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 ImpairmentEXPERIMENTALParticipants 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 functionEXPERIMENTALParticipants 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).
Sacituzumab Govitecan-hziy (SG) 8 mg/kgEXPERIMENTALParticipants 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/kgEXPERIMENTALParticipants 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/kgEXPERIMENTALParticipants 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/kgEXPERIMENTALParticipants 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.
Interventions
NameTypeDescription
Sacituzumab govitecan-hziyDRUGAdministered intravenously
DoxorubicinDRUGAdministered intravenously
PaclitaxelDRUGAdministered intravenously
Nab-paclitaxelDRUGAdministered intravenously
CapecitabineDRUGAdministered orally
Sacituzumab govitecan-hziy (SG)DRUGAdministered intravenously
PembrolizumabDRUGAdministered intravenously
GemcitabineDRUGAdministered intravenously
CarboplatinDRUGAdministered intravenously
DocetaxelDRUGAdministered intravenously
VinflunineDRUGAdministered intravenously
Eribulin Mesylate InjectionDRUGEribulin is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts.
Capecitabine Oral ProductDRUGCapecitabine is administered orally (PO) following recommended doses and regimens as per approved package inserts.
Gemcitabine InjectionDRUGGemcitabine is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts.
Vinorelbine injectionDRUGVinorelbine is administered by intravenous (IV) following recommended doses and regimens as per approved package inserts.
EribulinDRUGAdministered intravenously per NCCN guidelines
VinorelbineDRUGAdministered intravenously per NCCN guidelines
CisplatinDRUGAdministered intravenously
AvelumabDRUGAdministered per package insert
ZimberelimabDRUGAdministered intravenously
DomvanalimabDRUGAdministered intravenously
Enfortumab VedotinDRUGAdministered intravenously
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Eligibility Criteria
Age Range18 Years to N/A
SexFEMALE
Healthy VolunteersNo
Study Sites189

Key Inclusion Criteria: * Documented evidence of recurrent/persistent endometrial cancer (endometrial carcinoma or carcinosarcoma). * Up to 3 prior lines of systemic therapy for endometrial cancer, including systemic platinum-based chemotherapy and anti-PD-1/PD-L1 therapy, either in combination or ...

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