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)

Study summary

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

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Key things to know

Main goalTreatment

This describes the study’s primary purpose.

What is being studiedAdagrasib and Pembrolizumab

Plus 4 other study approaches.

Who it may be forNon-small cell lung cancer (NSCLC) · KRAS · Locally advanced

These are broad labels—not an eligibility decision.

Checked against the public recordLast updated Oct 13, 2026 · Source: ClinicalTrials.gov

Is enrollment open?Recruiting

The study is currently accepting participants.

What kind of study?Phase 3

Interventional

Where is it offered?351 U.S. locations

Locations may change over time.

Who runs it?Mirati Therapeutics Inc.

Study sponsor

Study overview

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

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How this study is categorized

These labels come from structured fields and exact terms in the public record.

Cancer type

Non-small cell lung cancer (NSCLC)→

Disease setting

Locally advanced→Metastatic or stage IV→

Biomarkers

KRAS→

Treatment approach

Immunotherapy→Targeted therapy→Chemotherapy→

Public criteria

Who may be able to participate

The sponsor separates these requirements into two groups. You do not need to interpret them alone—use them to guide a conversation with the study team.

Requirements people may need to meetInclusion 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.

Reasons someone may not be able to joinExclusion 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/

Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.

Study sites

U.S. locations

University of Alabama at BirminghamBirmingham, Alabama
Highlands Oncology Group - SpringdaleSpringdale, Arkansas
Providence Medical FoundationFullerton, California
Local Institution - 0682Loma Linda, California
Helios Clinical ResearchLong Beach, California
National Jewish Health Medical CenterDenver, Colorado
Medical Oncology Hematology Consultants, PANewark, Delaware
Morton Plant Hospital - BayCare Health SystemClearwater, Florida
Cancer Specialists of North FloridaJacksonville, Florida
Local Institution - 0696Miami, Florida
Ocala Oncology Center PL DBA Florida Cancer Affiliates - OcalaOcala, Florida
Mid Florida Hematology and Oncology CenterOrange City, Florida

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Oct 13, 2026. Always confirm current availability with the study team.

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