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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) | Clinical Trials | Clareo Health

RECRUITINGPHASE3

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)

A Randomized, Double-Blind, Phase 3 Trial of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated, Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

NCT06875310•Mirati Therapeutics Inc.

View on ClinicalTrials.gov

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

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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.

Locations (337)

Local Institution - 0347

Birmingham, Alabama, United States

Local Institution - 0686

Springdale, Arkansas, United States

Local Institution - 0581

Fullerton, California, United States

Local Institution - 0682

Loma Linda, California, United States

Local Institution - 0202

Long Beach, California, United States

Local Institution - 0623

Santa Barbara, California, United States

Local Institution - 0442

Denver, Colorado, United States

Local Institution - 0052

Jacksonville, Florida, United States

Local Institution - 0680

Ocala, Florida, United States

Local Institution - 0679

Orange City, Florida, United States

Key Dates

Start Date

April 24, 2025

Primary Completion Date

September 7, 2029

Completion Date

April 30, 2032

Last Updated

March 13, 2026

Enrollment

630

ESTIMATED participants

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Adagrasib

DRUG

Pembrolizumab

DRUG

Carboplatin

DRUG

Pemetrexed

DRUG

Placebo

DRUG

Cisplatin

DRUG

Contacts

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

CONTACT

855-907-3286 Clinical.Trials@bms.com

First line of the email MUST contain NCT # and Site #.

CONTACT

A Study of JNJ-90301900 in Combination With Chemoradiation Followed by Consolidation Immunotherapy for Non-Small Cell Lung Cancer (NSCLC)

NCT06667908

Carcinoma, Non-Small-Cell Lung

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RECRUITING

KEYMAKER-U01 Umbrella Master Study: Studies of Investigational Agents With Either Pembrolizumab (MK-3475) Alone or With Pembrolizumab PLUS Chemotherapy in Participants With Non-small Cell Lung Cancer (NSCLC) (MK-3475-U01/KEYMAKER-U01)

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Carcinoma, Non-Small-Cell Lung

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 13, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

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)

Inclusion Criteria

Exclusion Criteria

A Study of JNJ-90301900 in Combination With Chemoradiation Followed by Consolidation Immunotherapy for Non-Small Cell Lung Cancer (NSCLC)

KEYMAKER-U01 Umbrella Master Study: Studies of Investigational Agents With Either Pembrolizumab (MK-3475) Alone or With Pembrolizumab PLUS Chemotherapy in Participants With Non-small Cell Lung Cancer (NSCLC) (MK-3475-U01/KEYMAKER-U01)

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