Study of Sacituzumab Govitecan (SG) Versus Docetaxel in 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 compare the study drug, sacituzumab govitecan-hziy (SG), versus docetaxel in participants with advanced or metastatic (cancer that has spread) non-small cell lung cancer (NSCLC).

Official Title
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Open-Label, Global, Multicenter, Randomized, Phase 3 Study of Sacituzumab Govitecan Versus Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Progression on or After Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Immunotherapy

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Biological: Sacituzumab Govitecan-hziy (SG)
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Pathologically documented non-small cell lung cancer (NSCLC) with documented evidence of Stage 4 NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition). Epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) results are required. Testing prior to enrollment. Resulting for other actionable genomic alterations is recommended and to be performed as per local standard of care and availability of targeted treatment. For patients with squamous cell carcinoma, EGFR and ALK testing is optional. Must have progressed after platinum-based chemotherapy in combination with anti-PD-1/PD-L1 antibody OR platinum-based chemotherapy and anti-PD-1/PD-L1 antibody (in either order) sequentially. No additional treatments are allowed in the recurrent/metastatic setting for individuals with no actionable genomic alterations. Individuals with EGFR, ALK, or any other known actionable genomic alterations must have also received treatment with at least 1 locally approved and available tyrosine kinase inhibitor 1(TKI) appropriate to the genomic alteration. Documented radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC. Measurable disease based on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by the investigator in accordance with per RECIST Version 1.1. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 before randomization. Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count ≥ 1500/mm^3, and platelets ≥ 100,000/μL). Adequate hepatic function (bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate aminotransferase and alanine aminotransferase ≤ 2.5 ULN or ≤ 5 x ULN if known liver metastases, and serum albumin > 3 g/dL). Creatinine clearance of at least 30 mL/min as assessed by the Cockcroft-Gault equation. Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception. Key Exclusion Criteria: Mixed small-cell lung cancer and NSCLC histology. Positive serum pregnancy test or women who are lactating. Received a prior anticancer biologic agent within 4 weeks prior to enrollment or have received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrollment and have not recovered (ie, > Grade 2 is considered not recovered) from adverse events (AEs) at the time of study entry. Individuals participating in observational studies are eligible. Have not recovered (ie, > Grade 2 is considered not recovered) from AEs due to a previously administered agent. Previously received treatment with any of the following: Topoisomerase 1 inhibitors. Any agent including an antibody-drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase 1 Trop-2-targeted therapy Docetaxel as monotherapy or in combination with other agents Active second malignancy NSCLC that is eligible for definitive local therapy alone. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc); any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren syndrome, sarcoidosis, etc); or prior pneumonectomy. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Active cardiac disease Active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal perforation within 6 months of enrollment. Active serious infection requiring antibiotics. Positive HIV-1 or HIV-2 antibody with detectable viral load OR taking medications that may interfere with SN-38 metabolism. Positive for hepatitis B surface antigen. Individuals who test positive for hepatitis B core antibody will require hepatitis B virus DNA by quantitative polymerase chain reaction for confirmation of active disease. Positive hepatitis C antibody and detectable hepatitis C viral load. 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)<br>Participants will receive SG 10 mg/kg on Days 1 and 8 of a 21-day cycle (ie, 2 weekly doses plus 1 week without treatment) until progressive disease (PD), death, unacceptable toxicity, or another treatment discontinuation criterion is met. | Biological: Sacituzumab Govitecan-hziy (SG)<br>* Administered intravenously<br>* Other names: GS-0132;|
| Active Comparator: Docetaxel<br>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. | Drug: Docetaxel<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from the date of randomization until the date of death from any cause. | Up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) Assessed by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | PFS is defined as the time from the date of randomization until the date of objective disease progression (PD) or death from any cause, whichever occurs first. | Up to 30 months | 
| Objective Response Rate (ORR) Assessed by Investigator per RECIST Version 1.1 | 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 later. | Up to 30 months | 
| Duration of Response (DOR) Assessed by Investigator per RECIST Version 1.1 | DOR is defined as time from first documented CR or PR to the earlier of the first documented PD or death from any cause (whichever comes first) | Up to 30 months | 
| Disease Control Rate (DCR) Assessed by Investigator per RECIST Version 1.1 | DCR is defined as the proportion of participants who achieve a CR, PR, or stable disease (SD) as assessed by RECIST Version 1.1. | Up to 30 months | 
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) |  | First dose date up to 30 months plus 30 days | 
| Percentage of Participants Experiencing Laboratory abnormalities |  | First dose date up to 30 months plus 30 days | 
| Time to First Deterioration in Shortness of Breath Domain as Measured by Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Score | The NSCLC-SAQ is a patient reported outcome measure with seven items assessing five symptom concepts of NSCLC: cough, pain, dyspnea, fatigue, and appetite. Each item is rated using a five-point verbal rating scale from No <symptom> At All to Very severe <symptom> or from Never to Always, corresponding to a score of 0 to 4. The dyspnea (shortness of breath) item uses a Never to Always rating scale with higher score indicating higher frequency of dyspnea. | Up to 30 Months | 
| Time to First Deterioration in NSCLC-SAQ Total Score | The NSCLC-SAQ is a patient reported outcome measure with seven items assessing five symptom concepts of NSCLC: cough, pain, dyspnea, fatigue, and appetite. Each item is rated using a five-point verbal rating scale from No <symptom> At All to Very severe <symptom> or from Never to Always, corresponding to a score of 0 to 4. The sum of all 5 domain scores will be computed, if any scores are missing, a total score will not be computed. The total score ranges between 0 and 20 with higher scores indicating more severe symptoms. | Up to 30 Months |