Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer
Phase 3
Recruiting
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT05502237
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to compare the effect of zimberelimab (ZIM) and domvanalimab (DOM) in combination with chemotherapy relative to pembrolizumab (PEMBRO) in combination with chemotherapy on overall survival (OS) in patients with untreated metastatic non-small cell lung cancer with no actionable genomic alteration.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1069
Inclusion Criteria
-
Life expectancy ≥ 3 months.
-
Pathologically documented NSCLC that meets both of the criteria below:
- Have documented evidence of Stage IV NSCLC disease at the time of enrollment (based on American Joint Committee on Cancer (AJCC), Eighth Edition).
- Have documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations.
-
Have no actionable genomic alterations such as ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), RET mutations, or other driver oncogenes with approved frontline therapies.
-
Have not received prior systemic treatment for metastatic NSCLC.
-
Measurable disease per RECIST v1.1 criteria by investigator assessment.
-
Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1.
-
Have adequate organ functions.
Key
Exclusion Criteria
- Have mixed small-cell lung cancer (SCLC) and NSCLC histology.
- Positive serum pregnancy test or individuals who are breastfeeding or have plans to breastfeed during the study period.
- Received prior treatment with any anti-PD-1, anti-PD-L1, or any other antibody targeting an immune checkpoint.
- Known hypersensitivity to the study drug, its metabolites, or formulation excipient.
- Have an active second malignancy or have had an active second malignancy within 3 years prior to enrollment.
- Have an active autoimmune disease that required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
- Are receiving chronic systemic steroids.
- Have significant third-space fluid retention.
- Have untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or gastrointestinal perforation within 6 months of enrollment.
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Has had an allogenic tissue/solid organ transplant.
- Have received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu and COVID-19 vaccines that do not contain live virus are permitted.
- Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Zimberelimab (ZIM) + Chemotherapy Nab-paclitaxel Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy Nab-paclitaxel Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Pembrolizumab (PEMBRO) + Chemotherapy Nab-paclitaxel Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy Domvanalimab Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy Zimberelimab Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy Carboplatin Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy Cisplatin Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy Pemetrexed Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy Paclitaxel Participants will receive ZIM 360 mg + DOM 1200 mg (up to 35 doses) with chemotherapy every 3 weeks (Q3W) on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin area under the concentration versus time curve (AUC)5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Pembrolizumab (PEMBRO) + Chemotherapy Paclitaxel Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Pembrolizumab (PEMBRO) + Chemotherapy Pembrolizumab Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Pembrolizumab (PEMBRO) + Chemotherapy Carboplatin Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Pembrolizumab (PEMBRO) + Chemotherapy Cisplatin Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Pembrolizumab (PEMBRO) + Chemotherapy Pemetrexed Participants will receive PEMBRO 200 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles. After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) + Chemotherapy Zimberelimab Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) + Chemotherapy Carboplatin Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) + Chemotherapy Cisplatin Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) + Chemotherapy Paclitaxel Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles. Zimberelimab (ZIM) + Chemotherapy Pemetrexed Participants will receive ZIM 360 mg (up to 35 doses) with chemotherapy Q3W on Day 1 of each 21-day cycle. Choice of chemotherapy is dependent on histology. * Participants with nonsquamous histology will receive cisplatin 75 mg/m\^2 or carboplatin AUC 5 + pemetrexed 500 mg/m\^2 Q3W for first 4 cycles After the completion of the first 4 cycles, participants with nonsquamous histology may continue with maintenance pemetrexed 500 mg/m\^2 Q3W until disease progression or intolerable toxicities. * Participants with squamous histology will receive carboplatin AUC 6 Q3W with paclitaxel 200 mg/m\^2 Q3W or nab-paclitaxel 100 mg/m\^2 weekly (QW) for first 4 cycles.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) in Participants With Positive Programmed Cell Death-Ligand 1 (PD-L1) Expression (≥1%Tumor Cells) and in all Randomized Participants. Up to 68 months OS is defined as the time from the date of randomization to the date of death from any cause.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1 Up to 50 Months DOR is defined as the time from the first response (CR or PR), to the first documented PD or death from any cause, whichever comes first.
Time to First Symptom Deterioration in Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score Baseline, Up to 50 Months 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.
Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Upt to 50 months PFS is defined as the time from the date of randomization until disease progression (PD) or death from any cause, whichever comes first.
Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1 Up to 50 Months ORR is defined as the proportion of participants who have achieved a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later.
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) First dose date up to 50 months plus 30 days Percentage of Participants Experiencing Clinical Laboratory Abnormalities First dose date up to 50 months plus 30 days
Trial Locations
- Locations (226)
George Washington Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
Shanghai East Hospital
🇨🇳Shanghai, China
Palo Verde Hematology Oncology Ltd
🇺🇸Glendale, Arizona, United States
California Cancer Associates for Research and Excellence
🇺🇸San Marcos, California, United States
Texas Oncology
🇺🇸Dallas, Texas, United States
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Eastern CT Hematology and Oncology Associates
🇺🇸Norwich, Connecticut, United States
Lake City Cancer Care
🇺🇸Lake City, Florida, United States
Florida Cancer Specialists
🇺🇸Sarasota, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Scroll for more (216 remaining)George Washington Medical Faculty Associates🇺🇸Washington, District of Columbia, United States