A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)
This is a trial to evaluate the efficacy, safety, and tolerability of adagrasib plus pembrolizumab plus platinum-doublet chemotherapy versus placebo plus pembrolizumab plus platinum-doublet chemotherapy in participants with previously untreated, locally advanced or metastatic NSCLC with KRAS G12C mutation
Checked against the public recordLast updated Aug 14, 2026 · Source: ClinicalTrials.gov
What this study is about
- Purpose
- Treatment
- Study type
- Interventional
- Phase
- Phase 3
- Sponsor
- Mirati Therapeutics Inc.
- Interventions being studied
- Drug: Adagrasib; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Pemetrexed; Drug: Placebo; Drug: Cisplatin
How this study is categorized
These labels come from structured fields and exact terms in the public record.
Who may be able to participate
Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor sample and/or circulating tumor deoxyribonucleic acid (ctDNA). * Locally advanced or metastatic disease. * Measurable disease via computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria of at least 1 lesion. * No prior systemic anti-cancer therapy given for advanced or metastatic disease. * Not a candidate for definitive therapy (eg, chemoradiation or complete surgical resection). * Participants with brain metastases are eligible for enrollment, including those with untreated brain metastases. Brain metastases must be asymptomatic and not in need of immediate local therapy. Any untreated brain metastases must be ≤ 20 mm in diameter. * Any PD-L1 expression (0 to 100%) as determined by VENTANA PD-L1 (SP263) assay, Agilent PD-L1 IHC 22C3 pharmDx, or Agilent PD-L1 IHC 28-8 pharmDx. Exclusion Criteria: * Participants with an active autoimmune or inflammatory disease requiring systemic treatment within 2 years. * Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment that are ongoing or with risk of recurrence. * Inadequate bone marrow or liver function or electrocardiogram (ECG) abnormalities. * Ongoing treatment with concomitant medication known to cause prolonged QTc interval and that cannot be switched to alternative treatment prior to study entry. * Treatment targeting KRAS G12C mutation (eg, sotorasib, adagrasib) in any setting. * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration. * Other protocol-defined Inclusion/Exclusion criteria apply.
Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.
U.S. locations
- Local Institution - 0347Birmingham, Alabama
- Local Institution - 0686Springdale, Arkansas
- Local Institution - 0581Fullerton, California
- Local Institution - 0682Loma Linda, California
- Helios Clinical ResearchLong Beach, California
- National Jewish Health Medical CenterDenver, Colorado
- Medical Oncology Hematology Consultants, PANewark, Delaware
- Local Institution - 0694Clearwater, Florida
- Cancer Specialists of North FloridaJacksonville, Florida
- Local Institution - 0696Miami, Florida
- Local Institution - 0680Ocala, Florida
- Mid Florida Hematology and Oncology CenterOrange City, Florida
Source and freshness
Processed from ClinicalTrials.gov. Last public update: Aug 14, 2026. Always confirm current availability with the study team.