STAR-121: Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy in Patients With Untreated Metastatic Non-Small Cell Lung Cancer

Sponsor

Gilead Sciences (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05502237

Collaborator

Arcus Biosciences, Inc. (Industry)

720

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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 progression-free survival (PFS) and overall survival (OS) in patients with untreated metastatic non-small cell lung cancer with no actionable genomic alteration.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Drug: Zimberelimab Drug: Domvanalimab Drug: Pembrolizumab Drug: Carboplatin Drug: Cisplatin Drug: Paclitaxel Drug: Nab-paclitaxel Drug: Pemetrexed	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

720 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized, Open-Label, Phase 3 Study to Evaluate Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy for the First-Line Treatment of Patients With Metastatic Non-Small Cell Lung Cancer With No Epidermal Growth Factor Receptor or Anaplastic Lymphoma Kinase Genomic Tumor Aberrations

Anticipated Study Start Date :

Oct 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2027

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy 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.	Drug: Zimberelimab Administered intravenously Other Names: GS-0122 AB-122 Drug: Domvanalimab Administered intravenously Other Names: GS-0154 AB-154 Drug: Carboplatin Administered intravenously Drug: Cisplatin Administered intravenously Drug: Paclitaxel Administered intravenously Drug: Nab-paclitaxel Administered intravenously Drug: Pemetrexed Administered intravenously
Active Comparator: Pembrolizumab (PEMBRO) + Chemotherapy 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.	Drug: Pembrolizumab Administered intravenously Other Names: Keytruda® Drug: Carboplatin Administered intravenously Drug: Cisplatin Administered intravenously Drug: Paclitaxel Administered intravenously Drug: Nab-paclitaxel Administered intravenously Drug: Pemetrexed Administered intravenously
Experimental: Zimberelimab (ZIM) + Chemotherapy 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.	Drug: Zimberelimab Administered intravenously Other Names: GS-0122 AB-122 Drug: Carboplatin Administered intravenously Drug: Cisplatin Administered intravenously Drug: Paclitaxel Administered intravenously Drug: Nab-paclitaxel Administered intravenously Drug: Pemetrexed Administered intravenously

Arm

Intervention/Treatment

Experimental: Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy

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.

Drug: Zimberelimab

Administered intravenously

Other Names:

GS-0122

AB-122

Drug: Domvanalimab

Administered intravenously

Other Names:

GS-0154

AB-154

Drug: Carboplatin

Administered intravenously

Drug: Cisplatin

Administered intravenously

Drug: Paclitaxel

Administered intravenously

Drug: Nab-paclitaxel

Administered intravenously

Drug: Pemetrexed

Administered intravenously

Active Comparator: Pembrolizumab (PEMBRO) + Chemotherapy

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.

Drug: Pembrolizumab

Administered intravenously

Other Names:

Keytruda®

Drug: Carboplatin

Administered intravenously

Drug: Cisplatin

Administered intravenously

Drug: Paclitaxel

Administered intravenously

Drug: Nab-paclitaxel

Administered intravenously

Drug: Pemetrexed

Administered intravenously

Experimental: Zimberelimab (ZIM) + Chemotherapy

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.

Drug: Zimberelimab

Administered intravenously

Other Names:

GS-0122

AB-122

Drug: Carboplatin

Administered intravenously

Drug: Cisplatin

Administered intravenously

Drug: Paclitaxel

Administered intravenously

Drug: Nab-paclitaxel

Administered intravenously

Drug: Pemetrexed

Administered intravenously

Outcome Measures

Primary Outcome Measures

Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [Up to 31 months]
PFS is defined as the time from the date of randomization until disease progression (PD) or death from any cause, whichever comes first.
Overall Survival (OS) [Up to 58 months]
OS is defined as the time from the date of randomization to the date of death from any cause.

Secondary Outcome Measures

Objective Response Rate (ORR) as Assessed by BICR per RECIST Version 1.1 [Up to 58 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.
Duration of Response (DOR) as Assessed by BICR per RECIST Version 1.1 [Up to 58 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.
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [First dose date up to 58 months plus 30 days]
Percentage of Participants Experiencing Clinical Laboratory Abnormalities [First dose date up to 58 months plus 30 days]
Time to First Symptom Deterioration in Non-small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score [Baseline, Up to 58 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key 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 known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), RET mutations, or other actionable driver oncogenes with approved therapies (actionable genomic alteration).
Have not received prior systemic treatment for metastatic NSCLC.
Measurable disease by CT or MRI as 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 (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
Are receiving chronic systemic steroids.
Have significant third-space fluid retention
Have known active 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