Combination Therapies With Adagrasib in Patients With Advanced NSCLC With KRAS G12C Mutation (202200050434)

June 18, 2026 updated by: Mirati Therapeutics Inc.

A Phase 2 Trial of Combination Therapies With Adagrasib in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

Study CA239-0010 is an open-label, Phase 2 clinical trial evaluating the clinical efficacy of adagrasib in combination with pembrolizumab and chemotherapy in the first-line setting for patients with advanced NSCLC with TPS ≥ 1%, TPS <50% and KRAS G12C mutation

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Phase 2

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49055
        • Local Institution - 017-689
      • Caen, France, 14076
        • Local Institution - 017-196
      • Créteil, France, 94000
        • Local Institution - 017-190
      • Dijon, France, 21079
        • Local Institution - 017-192
      • La Tronche, France, 38700
        • Local Institution - 017-683
      • Marseille, France, 13009
        • Local Institution - 017-199
      • Paris, France, 75020
        • Local Institution - 017-686
      • Suresnes, France, 92150
        • Local Institution - 017-667
      • Toulouse, France, 31059
        • Local Institution - 017-663
      • Villejuif, France, 94805
        • Local Institution - 017-202
  • Greece
      • Heraklion, Greece, 71110
        • Local Institution - 017-238
      • Larissa, Greece, 41110
        • Local Institution - 017-235
      • Piraeus, Greece, 185 47
        • Local Institution - 017-234
  • Hungary
      • Budapest, Hungary, 1121
        • Local Institution - 017-244
      • Budapest, Hungary, 1122
        • Local Institution - 017-241
      • Székesfehérvár, Hungary, 8000
        • Local Institution - 017-759
      • Törökbálint, Hungary, 2045
        • Local Institution - 017-240
  • Italy
      • Avellino, Italy, 83100
        • Local Institution - 017-292
      • Casale Monferrato, Italy, 15033
        • Local Institution - 017-773
      • Florence, Italy, 50134
        • Local Institution - 017-762
      • Milan, Italy, 20141
        • Local Institution - 017-278
      • Orbassano, Italy, 10043
        • Local Institution - 017-788
      • Ravenna, Italy, 48121
        • Local Institution - 017-767
      • Roma, Italy, 00144
        • Local Institution - 017-295
  • Poland
      • Lodz, Poland, 90-302
        • Local Institution - 017-757
      • Poznan, Poland, 60-639
        • Local Institution - 017-382
      • Warsaw, Poland, 04-349
        • Local Institution - 017-774
  • Spain
      • A Coruña, Spain, 15006
        • Local Institution - 017-613
      • Madrid, Spain, 28007
        • Local Institution - 017-619
      • Madrid, Spain, 28046
        • Local Institution - 017-624
      • Majadahonda, Spain, 28222
        • Local Institution - 017-626
      • Palma de Mallorca, Spain, 07120
        • Local Institution - 017-602
      • Palma de Mallorca, Spain, 07198
        • Local Institution - 017-771
      • Seville, Spain, 41009
        • Local Institution - 017-772
      • Zaragoza, Spain, 50009
        • Local Institution - 017-603
  • United States
    • California
      • Fountain Valley, California, United States, 92708
        • Local Institution - 017-936C
      • Fountain Valley, California, United States, 92708
        • Local Institution - 017-936
      • Fullerton, California, United States, 92835
        • Local Institution - 017-851
      • San Francisco, California, United States, 94158
        • Local Institution - 017-540
    • Colorado
      • Aurora, Colorado, United States, 80012
        • Local Institution - 017-872-I
      • Boulder, Colorado, United States, 80303
        • Local Institution - 017-872-G
      • Colorado Springs, Colorado, United States, 80907
        • Local Institution - 017-872-D
      • Colorado Springs, Colorado, United States, 80920
        • Local Institution - 017-872-J
      • Denver, Colorado, United States, 80218
        • Local Institution - 017-872-B
      • Denver, Colorado, United States, 80220
        • Local Institution - 017-872-F
      • Lakewood, Colorado, United States, 80228
        • Local Institution - 017-872-A
      • Littleton, Colorado, United States, 80218
        • Local Institution - 017-872-C
      • Lone Tree, Colorado, United States, 80124
        • Local Institution - 017-872
      • Pueblo, Colorado, United States, 81003
        • Local Institution - 017-872-E
      • Thornton, Colorado, United States, 80260
        • Local Institution - 017-872-H
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Local Institution - 017-829
      • Lakeland, Florida, United States, 33812
        • Local Institution - 017-898
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Local Institution - 017-972
    • Kansas
      • Fairway, Kansas, United States, 66205
        • Local Institution - 017-820J
      • Kansas City, Kansas, United States, 66160
        • Local Institution - 017-820A
      • Kansas City, Kansas, United States, 66160
        • Local Institution - 017-820B
      • Kansas City, Kansas, United States, 66160
        • Local Institution - 017-820C
      • Kansas City, Kansas, United States, 66160
        • Local Institution - 017-820H
      • Overland Park, Kansas, United States, 66210
        • Local Institution - 017-820I
      • Westwood, Kansas, United States, 66205
        • Local Institution - 017-820
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 017-388
      • Boston, Massachusetts, United States, 02215
        • Local Institution - 017-808
    • Michigan
      • Novi, Michigan, United States, 48377
        • Local Institution - 017-811
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Local Institution - 017-838B
      • Minneapolis, Minnesota, United States, 55404
        • Local Institution - 017-838C
      • Rochester, Minnesota, United States, 55905
        • Local Institution - 017-830
      • Saint Louis Park, Minnesota, United States, 55416
        • Local Institution - 017-838
      • Saint Louis Park, Minnesota, United States, 55426-5000
        • Local Institution - 017-838A
    • Missouri
      • Kansas City, Missouri, United States, 64116
        • Local Institution - 017-820F
      • Kansas City, Missouri, United States, 64154
        • Local Institution - 017-820E
      • Lee's Summit, Missouri, United States, 64064
        • Local Institution - 017-820D
      • North Kansas City, Missouri, United States, 64116
        • Local Institution - 017-820G
    • New York
      • Babylon, New York, United States, 11702
        • Local Institution - 017-080
      • Brooklyn, New York, United States, 11210
        • Local Institution - 017-088
      • East Syracuse, New York, United States, 13057
        • Local Institution - 017-587
      • New Hyde Park, New York, United States, 11042
        • Local Institution - 017-087
      • New York, New York, United States, 10028
        • Local Institution - 017-085
      • Patchogue, New York, United States, 11772
        • Local Institution - 017-082
      • Port Jefferson, New York, United States, 11776
        • Local Institution - 017-086
      • Port Jefferson Station, New York, United States, 11776
        • Local Institution - 017-081
      • Port Jefferson Station, New York, United States, 11776
        • Local Institution - 017-535
      • Riverhead, New York, United States, 11901
        • Local Institution - 017-084
      • The Bronx, New York, United States, 10469
        • Local Institution - 017-083
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Local Institution - 017-818
    • Texas
      • Dallas, Texas, United States, 75246
        • Local Institution - 017-879
      • Longview, Texas, United States, 75601
        • Local Institution - 017-878
      • Palestine, Texas, United States, 75801
        • Local Institution - 017-878-B
      • Paris, Texas, United States, 75460
        • Local Institution - 017-878-C
      • Tyler, Texas, United States, 75702
        • Local Institution - 017-878-A
    • Virginia
      • Arlington, Virginia, United States, 22205
        • Local Institution - 017-814-A
      • Fairfax, Virginia, United States, 22031
        • Local Institution - 017-814
      • Gainesville, Virginia, United States, 20155
        • Local Institution - 017-814-B
      • Reston, Virginia, United States, 20190
        • Local Institution - 017-814-C
    • Washington
      • Bellingham, Washington, United States, 98225
        • Local Institution - 017-909

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Cohort A* (closed): Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (squamous or nonsquamous) KRASG12C mutation and histologically confirmed PD-L1 TPS ≥1%.

  • Cohort C: Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (non-squamous only) KRASG12C mutation and histologically confirmed PD-L1 TPS < 50% AND previously completed 4 cycles of standard-of-care platinum based induction chemotherapy with pembrolizumab AND experienced stable disease, partial response, or complete response per investigator's assessment after 4 cycles OR if patients received <4 cycles of a platinum-based induction, was stopped early due to intolerable toxicity
  • Cohort E: Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (non-squamous only) KRASG12C mutation and histologically confirmed PD-L1 TPS < 50%
  • Presence of measurable disease per RECIST v1.1

Exclusion Criteria:

  • All Cohorts: Any prior therapy targeting KRASG12C mutation in any setting
  • Cohorts A & E: Prior systemic therapy for locally advanced or metastatic NSCLC, including chemotherapy, immune checkpoint inhibitor therapy or chemoimmunotherapy (note: prior systemic therapy or chemoradiation given in the adjuvant or neoadjuvant setting are allowed if last dose of prior systemic treatment was >1 year prior to first dose of study treatment)
  • Cohort C: received maintenance therapy (e.g, pembrolizumab and/or pemetrexed following completion of 4-6 cycles of a platinum-based regimen administered in the first-line setting
  • Radiation to the lung > 30 Gy within 6 months prior to first dose of study treatment
  • Active brain metastases

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort A: PD-L1 TPS≥ 1% (Closed)
Adagrasib 400 mg BID for 2 cycles followed by adagrasib 400 mg BID + pembrolizumab 200 mg every 3 weeks (Q3W) up to 35 cycles
Drug: Adagrasib oral dose of 400 mg twice daily tablets
oral dose of 400 mg twice daily tablets
Experimental: Cohort C
Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles
Drug: Adagrasib oral dose of 400 mg twice daily tablets
oral dose of 400 mg twice daily tablets
Combination product: Pembrolizumab
IV infusion once every 3 weeks
Combination product: Chemotherapy: Pemetrexed
IV infusion once every 3 weeks
Combination product: Cisplatin/Carboplatin
IV infusion once every 3 weeks
Experimental: Cohort E
Adagrasib 400 mg BID + pembrolizumab 200 mg Q3W + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 Q3W OR carboplatin AUC 5 Q3W for 4 cycles, followed by adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W (up to 31 cycles)
Drug: Adagrasib oral dose of 400 mg twice daily tablets
oral dose of 400 mg twice daily tablets
Combination product: Pembrolizumab
IV infusion once every 3 weeks
Combination product: Chemotherapy: Pemetrexed
IV infusion once every 3 weeks
Combination product: Cisplatin/Carboplatin
IV infusion once every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) for Cohort A and E
Time Frame: 30 months
Defined as the percent of patients documented to have a confirmed CR or PR
30 months
Progression-free Survival (PFS) at six months for Cohort C
Time Frame: 30 months
PFS is defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: 30 months
Defined as number of patients with treatment emergent AEs
30 months
Duration of Response (DOR)
Time Frame: 30 months
Defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first.
30 months
Overall Survival (OS)
Time Frame: 30 months
Defined as time from date of first study treatment to date of death due to any cause
30 months
Progression-free Survival (PFS)
Time Frame: 30 months
Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
30 months
Population pharmacokinetic (PK) Model Derived AUC at Steady State (AUCtau,ss).
Time Frame: Time Frame: Pre-dose and 4-6 hours post dose; up to 6 months
Concentration data from this study will be pooled with other studies and exposure parameters derived using population PK methods. Data for this Outcome Measure will not be reported here since ClinicalTrials.gov is designed to report results from participants enrolled in the study and described in the Participant Flow module.
Time Frame: Pre-dose and 4-6 hours post dose; up to 6 months
Cohorts C and E: DLTs during SLI (Safety Lead In)
Time Frame: 30 months
Defined as those patients in the SLI of the study who have received at least 80% of the assigned dose of adagrasib during the first cycle on study, or interrupted or discontinued study treatment during the first cycle due to a DLT.
30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mirati Therapeutics Inc.

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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 Major Dates

Study Start (Actual)

November 22, 2022

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

November 1, 2022

First Submitted That Met QC Criteria

November 1, 2022

First Posted (Actual)

November 8, 2022

Study Record Updates

Last Update Posted (Actual)

June 23, 2026

Last Update Submitted That Met QC Criteria

June 18, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA239-0010 (Other Identifier: Bristol-Myers Squibb Protocol ID)
  • 849-017 (Other Identifier: Mirati Therapeutics Protocol ID)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html

IPD Sharing Time Frame

See Plan Description

IPD Sharing Access Criteria

See Plan Description

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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