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RecruitingInterventionalPhase 3

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)

NCT ID: NCT06875310Sponsor: Mirati Therapeutics Inc.Last updated: 2026-06-02

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

Arms & interventions

  • DrugAdagrasib

    Specified dose on specified days

  • DrugPembrolizumab

    Specified dose on specified days

  • DrugCarboplatin

    Specified dose on specified days

  • DrugPemetrexed

    Specified dose on specified days

  • DrugPlacebo

    Specified dose on specified days

  • DrugCisplatin

    Specified dose on specified days

Outcome measures

Primary

  • Progression Free Survival (PFS) as Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Blinded Independent Central Review (BICR)

    Time frame: Up to 7 years

  • Overall Survival (OS)

    Time frame: Up to 7 years

Secondary

  • Overall Response (OR) as Assessed per RECIST v1.1 by BICR

    Time frame: Up to 7 years

  • Duration of Response (DOR) as Assessed per RECIST 1.1 by BICR

    Time frame: Up to 7 years

  • PFS as Assessed per RECIST v1.1 by Investigator

    Time frame: Up to 7 years

  • Number of Participants With Adverse Events (AEs)

    Time frame: Up to 90 days from last dose

  • Number of Participants With Serious Adverse Events (SAEs)

    Time frame: Up to 90 days from last dose

  • Number of Participants With AEs Leading to Dose Interruption

    Time frame: Up to 90 days from last dose

  • Number of Participants With AEs Leading to Dose Reduction

    Time frame: Up to 90 days from last dose

  • Number of Participants With AEs Leading to Treatment Discontinuation

    Time frame: Up to 90 days from last dose

  • Number of Deaths

    Time frame: Up to 90 days from last dose

  • Time to Definitive Deterioration by Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ) Total Score

    Time frame: Up to 7 years

  • Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) Scale/item Score

    Time frame: Up to 90 days from last dose

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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.

Study locations (54)

Local Institution - 0347

Birmingham, Alabama, 35294

Not Yet Recruiting
Site 0347 · Contact

Local Institution - 0686

Springdale, Arkansas, 72762

Not Yet Recruiting
Site 0686 · Contact

Local Institution - 0581

Fullerton, California, 92835

Not Yet Recruiting
Site 0581 · Contact

Local Institution - 0682

Loma Linda, California, 92354

Not Yet Recruiting
Site 0682 · Contact

Helios Clinical Research

Long Beach, California, 90805

Recruiting
Omkar Marathe, Site 0202 · Contact

Local Institution - 0442

Denver, Colorado, 80206

Not Yet Recruiting
Site 0442 · Contact

Local Institution - 0701

Newark, Delaware, 19713

Not Yet Recruiting
Site 0701 · Contact

Local Institution - 0694

Clearwater, Florida, 33756

Not Yet Recruiting
Site 0694 · Contact

Cancer Specialists of North Florida

Jacksonville, Florida, 32256

Recruiting
Laura Lourdes, Site 0052 · Contact

Local Institution - 0696

Miami, Florida, 33176

Not Yet Recruiting
Site 0696 · Contact

Local Institution - 0680

Ocala, Florida, 34474

Not Yet Recruiting
Site 0680 · Contact

Mid Florida Hematology and Oncology Center

Orange City, Florida, 32763

Recruiting
Santosh Nair, Site 0679 · Contact

Cancer Care Centers of Brevard, Inc.

Palm Bay, Florida, 32901

Recruiting
venkat pavan kancharla, Site 0621 · Contact

Florida Clinical Trials Group.

Plantation, Florida, 33322

Recruiting
Harshad Amin, Site 0365 · Contact

Local Institution - 0695

St. Petersburg, Florida, 33705

Not Yet Recruiting
Site 0695 · Contact

Florida Clinical Trials Group.

Tamarac, Florida, 33321

Recruiting
Chintan Gandhi, Site 0377 · Contact

Local Institution - 0647

Tampa, Florida, 33612

Not Yet Recruiting
Site 0647 · Contact

Local Institution - 0699

Tampa, Florida, 33612

Not Yet Recruiting
Site 0699 · Contact

Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital

Marietta, Georgia, 30060

Recruiting
Walid Shaib, Site 0031 · Contact

Illinois Cancer Specialists

Arlington Heights, Illinois, 60005

Recruiting
David Hakimian, Site 0665 · Contact

Local Institution - 0676

Chicago, Illinois, 60612

Not Yet Recruiting
Site 0676 · Contact

Local Institution - 0683

Springfield, Illinois, 62703

Not Yet Recruiting
Site 0683 · Contact

Local Institution - 0454

Dyer, Indiana, 46311

Not Yet Recruiting
Site 0454 · Contact

Local Institution - 0684

Fort Wayne, Indiana, 46845

Not Yet Recruiting
Site 0684 · Contact

Local Institution - 0423

Munster, Indiana, 46321

Withdrawn

Mercy Medical Center

Cedar Rapids, Iowa, 52403

Recruiting
Ann Stroh, Site 0691 · Contact

Local Institution - 0366

Edgewood, Kentucky, 41017

Not Yet Recruiting
Site 0366 · Contact

Local Institution - 0566

Louisville, Kentucky, 40202

Not Yet Recruiting
Site 0566 · Contact

Local Institution - 0693

Owensboro, Kentucky, 42303

Not Yet Recruiting
Site 0693 · Contact

Local Institution - 0698

Paducah, Kentucky, 42003

Not Yet Recruiting
Site 0698 · Contact

Local Institution - 0644

Shreveport, Louisiana, 71103

Not Yet Recruiting
Site 0644 · Contact

Local Institution - 0702

Annapolis, Maryland, 21401

Not Yet Recruiting
Site 0702 · Contact

Maryland Oncology Hematology - Columbia

Columbia, Maryland, 21044

Recruiting
Mohit Narang, Site 0385 · Contact

Local Institution - 0019

Boston, Massachusetts, 02215

Not Yet Recruiting
Site 0019 · Contact

Local Institution - 0293

Detroit, Michigan, 48201

Not Yet Recruiting
Site 0293 · Contact

Local Institution - 0685

Fenton, Missouri, 63026

Not Yet Recruiting
Site 0685 · Contact

Local Institution - 0678

Cooperstown, New York, 13326

Not Yet Recruiting
Site 0678 · Contact

Local Institution - 0689

Rochester, New York, 14642

Not Yet Recruiting
Site 0689 · Contact

Ellis Hospital

Schenectady, New York, 12308

Recruiting
Tallat Mahmood, Site 0634 · Contact

Local Institution - 0618

White Plains, New York, 10601

Not Yet Recruiting
Site 0618 · Contact

Local Institution - 0624

Asheville, North Carolina, 28806

Not Yet Recruiting
Site 0624 · Contact

Local Institution - 0672

Salisbury, North Carolina, 28144

Not Yet Recruiting
Site 0672 · Contact

Local Institution - 0688

Easton, Pennsylvania, 18045

Not Yet Recruiting
Site 0688 · Contact

Local Institution - 0376

Hershey, Pennsylvania, 17033

Not Yet Recruiting
Site 0376 · Contact

WellSpan Oncology Research

York, Pennsylvania, 17403

Recruiting
Ikechukwu Akunyili, Site 0657 · Contact

Local Institution - 0681

Greenville, South Carolina, 29605

Withdrawn

Local Institution - 0658

Greenville, South Carolina, 29607

Not Yet Recruiting
Site 0658 · Contact

SCRI Oncology Partners

Nashville, Tennessee, 37203

Recruiting
David Spigel, Site 0020 · Contact

Local Institution - 0697

Nashville, Tennessee, 37212

Not Yet Recruiting
Site 0697 · Contact

Local Institution - 0034

Dallas, Texas, 75246

Not Yet Recruiting
Site 0034 · Contact

Local Institution - 0692

Galveston, Texas, 77555

Not Yet Recruiting
Site 0692 · Contact

Local Institution - 0652

Laredo, Texas, 78041

Not Yet Recruiting
Site 0652 · Contact

Texas Oncology - San Antonio

San Antonio, Texas, 78217

Recruiting
Krishna Alluri, Site 0622 · Contact

Local Institution - 0700

Tyler, Texas, 75702

Not Yet Recruiting
Site 0700 · Contact