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Comparing two treatments for untreated metastatic non-small cell lung cancer

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

Phase 3 Interventional Gilead Sciences · NCT05502237

This study is testing whether a new combination of treatments for lung cancer can help people with advanced non-small cell lung cancer live longer compared to a standard treatment.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment1069 (estimated)
Ages18 Years and up
SexAll
SponsorGilead Sciences Industry-sponsored
Drugs / interventionszimberelimab, domvanalimab, pembrolizumab, chemotherapy
Locations225 sites (Glendale, Arizona and 224 other locations)
Trial IDNCT05502237 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the effectiveness of zimberelimab and domvanalimab combined with chemotherapy against pembrolizumab combined with chemotherapy in patients with untreated metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations. The primary focus is on overall survival rates among participants. Eligible patients must have stage IV NSCLC and meet specific criteria regarding prior treatments and genetic mutations. The study is designed to provide insights into potential new treatment options for this patient population.

Who should consider this trial

Good fit: Ideal candidates are patients with untreated stage IV non-small cell lung cancer who do not have actionable genomic alterations.

Not a fit: Patients with mixed small-cell lung cancer and non-small cell lung cancer histology may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a new effective treatment option for patients with untreated metastatic non-small cell lung cancer.

How similar studies have performed: Other studies have shown promise in using similar immunotherapy approaches for lung cancer, indicating potential for success in this trial.

Eligibility criteria

Show full inclusion / 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.

Where this trial is running

Glendale, Arizona and 224 other locations

+175 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-small Cell Lung Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.