RECRUITING

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)

Conditions

Carcinoma, Non-Small-Cell Lung Immunotherapy KRAS KRAS G12C Targeted therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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)

Quick Facts

Study Start:2025-04-30

Study Completion:2032-04-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06875310

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Histologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor tissue 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.	* Participants with an active, known, prior documented, or suspected autoimmune or inflammatory disease. * Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment. * 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.

Inclusion Criteria

Exclusion Criteria

* Histologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor tissue 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.

* Participants with an active, known, prior documented, or suspected autoimmune or inflammatory disease.
* Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment.
* 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.

Contacts and Locations

Study Contact

BMS Clinical Trials Contact Center www.BMSClinicalTrials.com

CONTACT

855-907-3286

Clinical.Trials@bms.com

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

CONTACT

Study Locations (Sites)

Local Institution - 0347

Birmingham, Alabama, 35294-3300

United States

Local Institution - 0581

Fullerton, California, 92835

United States

Local Institution - 0202

Long Beach, California, 90805

United States

Local Institution - 0643

Newport Beach, California, 92663

United States

Local Institution - 0666

Orange, California, 92868

United States

Local Institution - 0623

Santa Barbara, California, 93105

United States

Local Institution - 0442

Denver, Colorado, 80206

United States

Local Institution - 0651

Gainesville, Florida, 32610

United States

Local Institution - 0621

Palm Bay, Florida, 32901

United States

Local Institution - 0377

Tamarac, Florida, 33321

United States

Local Institution - 0647

Tampa, Florida, 33612

United States

Local Institution - 0392

Fort Eisenhower, Georgia, 30905

United States

Local Institution - 0031

Marietta, Georgia, 30060

United States

Local Institution - 0665

Arlington Heights, Illinois, 60005

United States

Local Institution - 0423

Munster, Indiana, 46321

United States

Local Institution - 0366

Edgewood, Kentucky, 41017

United States

Local Institution - 0566

Louisville, Kentucky, 40202

United States

Local Institution - 0644

Shreveport, Louisiana, 71103

United States

Local Institution - 0385

Columbia, Maryland, 21044

United States

Local Institution - 0019

Boston, Massachusetts, 02215

United States

Local Institution - 0437

Worcester, Massachusetts, 01655

United States

Local Institution - 0618

White Plains, New York, 10601

United States

Local Institution - 0624

Asheville, North Carolina, 28806

United States

Local Institution - 0620

Columbus, Ohio, 43219

United States

Local Institution - 0657

York, Pennsylvania, 17403

United States

Local Institution - 0658

Greenville, South Carolina, 29607

United States

Local Institution - 0652

Laredo, Texas, 78041

United States

Local Institution - 0622

San Antonio, Texas, 78217

United States

Collaborators and Investigators

Sponsor: Mirati Therapeutics Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2025-04-30

Study Completion Date2032-04-30

Study Record Updates

Study Start Date2025-04-30

Study Completion Date2032-04-30

Terms related to this study

Keywords Provided by Researchers

Immunotherapy
KRAS
KRAS G12C
Targeted therapy

Additional Relevant MeSH Terms

Carcinoma, Non-Small-Cell Lung