Study of Sacituzumab Govitecan Combinations in First-line Treatment of Participants With Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The goal of this clinical study is to learn more about the study drug, sacituzumab govitecan-hziy (SG), and its dosing in combination with pembrolizumab or pembrolizumab and a platinum agent (carboplatin or cisplatin), in participants with advanced or metastatic (cancer that has spread) non-small-cell lung cancer (NSCLC).

Official Title
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An Open-label, Multicenter, Phase 2 Study of Sacituzumab Govitecan Combinations in First-line Treatment of Patients With Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC) Without Actionable Genomic Alterations

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Sacituzumab Govitecan-hziy (SG)
* Drug: Pembrolizumab
* Drug: Carboplatin
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Individuals with pathologically documented evidence of Stage IV non-small cell lung Cancer (NSCLC) disease at the time of enrollment Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST Version 1.1 criteria by investigator No prior systemic treatment for metastatic NSCLC Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Adequate hematologic counts Adequate hepatic function Key Exclusion Criteria: Mixed SCLC and NSCLC histology Active second malignancy NSCLC that is eligible for definitive local therapy alone Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy Has an active autoimmune disease that has required systemic treatment in past 2 years Has had an allogenic tissue/solid organ transplant. Has severe (≥ Grade 3) hypersensitivity to SG, pembrolizumab, carboplatin, or cisplatin, their metabolites, or formulation excipient Has received radiation therapy to the lung Individuals may not have received systemic anticancer treatment within the previous 6 months Is currently participating in or has participated in a study of an investigational agent Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses Known active central nervous system (CNS) metastases History of cardiac disease Active chronic inflammatory bowel disease Active serious infection requiring antibiotics Active or chronic hepatitis B infection Positive hepatitis C antibody Positive serum pregnancy test or women who are lactating Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sacituzumab Govitecan-hziy (SG) + Pembrolizumab (Cohort A)<br>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. | Drug: Sacituzumab Govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: IMMU-132;Drug: Pembrolizumab<br>* Administered intravenously<br>* Other names: Keytruda®;|
| Experimental: SG + Pembrolizumab (Cohort B)<br>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. | Drug: Sacituzumab Govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: IMMU-132;Drug: Pembrolizumab<br>* Administered intravenously<br>* Other names: Keytruda®;|
| Experimental: SG + Pembrolizumab + Carboplatin Safety Run-in<br>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. | Drug: Sacituzumab Govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: IMMU-132;Drug: Pembrolizumab<br>* Administered intravenously<br>* Other names: Keytruda®;Drug: Carboplatin<br>* Administered intravenously<br>* Other names: Paraplatin®;|
| Experimental: SG + Pembrolizumab + Cisplatin Safety Run-in (Optional)<br>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. | Drug: Sacituzumab Govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: IMMU-132;Drug: Pembrolizumab<br>* Administered intravenously<br>* Other names: Keytruda®;Drug: Cisplatin<br>* Administered intravenously<br>* Other names: Platinol®;|
| Experimental: SG + Pembrolizumab + Carboplatin or Cisplatin (Cohort C)<br>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. | Drug: Sacituzumab Govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: IMMU-132;Drug: Pembrolizumab<br>* Administered intravenously<br>* Other names: Keytruda®;Drug: Carboplatin<br>* Administered intravenously<br>* Other names: Paraplatin®;Drug: Cisplatin<br>* Administered intravenously<br>* Other names: Platinol®;|
| Experimental: SG + Pembrolizumab + Carboplatin or Cisplatin (Cohort D)<br>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. | Drug: Sacituzumab Govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: IMMU-132;Drug: Pembrolizumab<br>* Administered intravenously<br>* Other names: Keytruda®;Drug: Carboplatin<br>* Administered intravenously<br>* Other names: Paraplatin®;Drug: Cisplatin<br>* Administered intravenously<br>* Other names: Platinol®;|
| Experimental: SG + Pembrolizumab + Cisplatin (Cohort E)<br>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. | Drug: Sacituzumab Govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: IMMU-132;Drug: Pembrolizumab<br>* Administered intravenously<br>* Other names: Keytruda®;Drug: Cisplatin<br>* Administered intravenously<br>* Other names: Platinol®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival as Assessed by IRC per RECIST Version 1.1 |  | Up to 24 Months | 
| Overall Survival |  | Up to 24 Months | 
| Duration of Response as Assessed by IRC per RECIST Version 1.1 |  | Up to 24 Months | 
| Disease Control Rate as Assessed by IRC per RECIST Version 1.1 |  | Up to 24 Months | 
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) |  | First dose date up to 24 Months plus 30 days | 
| Percentage of Participants Experiencing Clinical Laboratory Abnormalities |  | First dose date up to 24 Months plus 30 days |