Study of Sacituzumab Govitecan (SG) Versus Docetaxel in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

Phase 3

Active, not recruiting

Conditions: Non-Small Cell Lung Cancer

Interventions: Biological: Sacituzumab Govitecan-hziy (SG)
Drug: Docetaxel

Registration Number: NCT05089734

Lead Sponsor: Gilead Sciences

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 603

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sacituzumab Govitecan-hziy (SG)	Sacituzumab Govitecan-hziy (SG)	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.
Docetaxel	Docetaxel	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.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to 24.4 months	OS is defined as the time from the date of randomization until the date of death from any cause. OS was estimated using Kaplan-Meier estimate. Participants without documentation of death were censored on the date they were last known to be alive.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) Assessed by Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	Up to 24.4 months	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 as assessed by RECIST v.1.1. As per RECIST 1.1, PD was defined as: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum measured while on study (this included the baseline sum if that was the smallest on study), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or the appearance of of 1 or more new lesions or unequivocal progression of existing non-target lesions. Participants who did not have documented disease progression and did not die were censored at their last tumor assessment date. Kaplan-Meier estimate was used for analysis.
Disease Control Rate (DCR) Assessed by Investigator Per RECIST Version 1.1	Up to 24.4 months	DCR was defined as the percentage of participants who achieved a CR, PR,or stable disease(SD)as assessed by RECIST v.1.1. Per RECIST 1.1 CR was disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal;PR was at least 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD,taking as reference the smallest sum LD since the treatment started and persistence of 1 or more nontarget lesion(s).PD was at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum measured while on study (this included the baseline sum if that was the smallest on study),in addition of increase of 20% sum also demonstrate an absolute increase of at least 5 mm or appearance of 1 or more new lesions or unequivocal progression of existing non-target lesions.
Time to First Deterioration in Shortness of Breath Domain as Measured by Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)	Up to 24.4 months	The NSCLC-SAQ is a participant reported outcome 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" depending on the item's question structure relative to either intensity or frequency, corresponding to a score of 0 to 4, with total score ranging from 0 to 20. The dyspnea (shortness of breath) item uses a "Never(0) to Always(4)" rating scale with higher score indicating higher frequency of dyspnea. Time to deterioration (TTD) was defined as the time from date of randomization to the first date a participant achieves 2-point deterioration from baseline. For shortness of breath domain, a 1-point or greater worsening from baseline represents a clinically meaningful deterioration. Kaplan-Meier estimate was used for analysis.
Objective Response Rate (ORR) Assessed by Investigator Per RECIST Version 1.1	Up to 24.4 months	ORR was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) that was confirmed at least 4 weeks later as assessed by RECIST v.1.1. As per RECIST 1.1 CR was defined as: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; PR was defined as: At least 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
Duration of Response (DOR) Assessed by Investigator Per RECIST Version 1.1	Up to 24.4 months	DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of PD or death from any cause (whichever comes first) as assessed by RECIST v. 1.1. As per RECIST 1.1 CR was disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; PR was at least 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD, and PD was at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum measured while on study (this included the baseline sum if that was the smallest on study), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or the appearance of of 1 or more new lesions or unequivocal progression of existing non-target lesions. Kaplan-Meier estimate was used for analysis.
Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)	Up to 3.5 years	An AE was defined as any untoward medical occurrence in a participants administered a medicinal product that does not necessarily have a causal relationship with this treatment. TEAEs were defined as any AEs that begin or worsen on or after the start of study drug through 30 days after the last dose of the study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0.
Percentage of Participants Who Experienced Grade 3 or 4 Treatment Emergent Laboratory Abnormalities Post-Baseline	Up to 3.5 years	Blood samples were collected for hematology, serum chemistry, and the laboratory abnormalities were assessed. A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the date of last study drug dose plus 30 days.The most severe graded abnormality observed post-baseline for each graded test was counted for each participant. Safety as assessed by grading of laboratory values and AEs according to the National Cancer Institutes' Common Terminology Criteria for Adverse Events (NCI CTCAE) covering grades 0-5 (0=Normal, 1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening, 5=Death). The percentage of participants with worst postbaseline grades 3 or 4 will be reported.
Time to First Deterioration in NSCLC-SAQ Total Score	Up to 24.4 months	The NSCLC-SAQ is a participant 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" depending on the item's question structure relative to either intensity or frequency, corresponding to a score of 0 to 4. A total score sums all five domain scores at each visit. If any domain score was missing, the score was not computed. The total score ranges between 0 and 20, with higher scores indicating more severe symptoms. TTD was defined as the time from date of randomization to the first date a participant achieves 2-point deterioration from baseline. For NSCLC-SAQ total score, a 2-point or greater worsening from baseline represents a clinically meaningful deterioration. Kaplan-Meier estimate was used for analysis.

Trial Locations

Locations (225): Alaska Oncology and Hematology, LLC.
🇺🇸
Anchorage, Alaska, United States
USOR - Arizona Oncology Associates Tucson - Wilmot
🇺🇸
Tucson, Arizona, United States
Beverly Hills Cancer Center
🇺🇸
Beverly Hills, California, United States
Rocky Mountain Cancer Centers - Aurora
🇺🇸
Aurora, Colorado, United States
Florida Cancer Specialists (Administration and Drug Shipment)
🇺🇸
Fort Myers, Florida, United States
Woodlands Medical Specialists, PA
🇺🇸
Pensacola, Florida, United States
Florida Cancer Specialists
🇺🇸
West Palm Beach, Florida, United States
University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
Illinois Cancer Specialists
🇺🇸
Niles, Illinois, United States
Siouxland Regional Cancer Center dba June E. Nylen Cancer Center
🇺🇸
Sioux City, Iowa, United States
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Alaska Oncology and Hematology, LLC.
🇺🇸Anchorage, Alaska, United States