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

Gilead Sciences

Status and phase

Active, not recruiting

Phase 3

Conditions

Non-small Cell Lung Cancer

Treatments

Drug: Domvanalimab

Drug: Nab-paclitaxel

Drug: Pembrolizumab

Drug: Paclitaxel

Drug: Cisplatin

Drug: Carboplatin

Drug: Pemetrexed

Drug: Zimberelimab

Study type

Interventional

Funder types

Industry

Identifiers

NCT05502237

2022-000578-25 (EudraCT Number)

GS-US-626-6216

Details and patient eligibility

About

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.

Enrollment

792 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

792 participants in 3 patient groups

Zimberelimab (ZIM) +Domvanalimab (DOM) + Chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Zimberelimab

Drug: Cisplatin

Drug: Carboplatin

Drug: Paclitaxel

Drug: Nab-paclitaxel

Drug: Domvanalimab

Pembrolizumab (PEMBRO) + Chemotherapy

Active Comparator group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Cisplatin

Drug: Carboplatin

Drug: Paclitaxel

Drug: Pembrolizumab

Drug: Nab-paclitaxel

Zimberelimab (ZIM) + Chemotherapy

Experimental group

Description:

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.

Treatment:

Drug: Pemetrexed

Drug: Zimberelimab

Drug: Cisplatin

Drug: Carboplatin

Drug: Paclitaxel

Drug: Nab-paclitaxel