RecruitingInterventionalPhase 2

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

NCT ID: NCT05609578Sponsor: Mirati Therapeutics Inc.Last updated: 2025-08-17

Summary

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

Arms & interventions

DrugAdagrasib oral dose of 400 mg twice daily tablets
oral dose of 400 mg twice daily tablets
Combination ProductPembrolizumab
IV infusion once every 3 weeks
Combination ProductChemotherapy: Pemetrexed
IV infusion once every 3 weeks
Combination ProductCisplatin/Carboplatin
IV infusion once every 3 weeks

Outcome measures

Primary

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

Secondary

Adverse Events
Time frame: 30 months
Duration of Response (DOR)
Time frame: 30 months
Overall Survival (OS)
Time frame: 30 months
Progression-free Survival (PFS)
Time frame: 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
Cohorts C and E: DLTs during SLI (Safety Lead In)
Time frame: 30 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

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 locations (84)

Local Institution - Unk025

Anchorage, Alaska, 99508

Active Not Recruiting

Local Institution - 017-591

Glendale, Arizona, 85304

Withdrawn

Local Institution - 017-821

Phoenix, Arizona, 85004

Withdrawn

Local Institution - Unk047

Anaheim, California, 92805

Active Not Recruiting

Local Institution - 017-936C

Fountain Valley, California, 92708

Not Yet Recruiting

Site 017-936C · Contact

MemorialCare - Orange Coast Medical Center

Fountain Valley, California, 92708

Recruiting

Amol Rao, Site 017-936 · Contact

510673-1293

Providence Medical Foundation - Virginia K. Crosson Cancer Center - Fullerton

Fullerton, California, 92835

Recruiting

David Park, Site 017-851 · Contact

714-446-5900

Local Institution - Unk004

Loma Linda, California, 92354

Active Not Recruiting

Local Institution - 017-961

Los Angeles, California, 90095

Withdrawn

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158

Recruiting

Collin Blakely, Site 017-540 · Contact

415-502-6959

Local Institution - 017-872-I

Aurora, Colorado, 80012

Not Yet Recruiting

Site 017-872-I · Contact

Local Institution - 017-872-G

Boulder, Colorado, 80303

Not Yet Recruiting

Site 017-872-G · Contact

Local Institution - 017-872-D

Colorado Springs, Colorado, 80907

Not Yet Recruiting

Site 017-872-D · Contact

Local Institution - 017-872-J

Colorado Springs, Colorado, 80920

Not Yet Recruiting

Site 017-872-J · Contact

Local Institution - 017-872-B

Denver, Colorado, 80218

Not Yet Recruiting

Site 017-872-B · Contact

Local Institution - 017-872-F

Denver, Colorado, 80220

Not Yet Recruiting

Site 017-872-F · Contact

Local Institution - 017-872-A

Lakewood, Colorado, 80228

Not Yet Recruiting

Site 017-872-A · Contact

Local Institution - 017-872-C

Littleton, Colorado, 80218

Not Yet Recruiting

Site 017-872-C · Contact

USOR - Rocky Mountain Cancer Centers - Lone Tree - Sky Ridge Medical Center

Lone Tree, Colorado, 80124

Recruiting

Robert Jotte, Site 017-872 · Contact

303-430-2700

Local Institution - 017-872-E

Pueblo, Colorado, 81003

Not Yet Recruiting

Site 017-872-E · Contact

Local Institution - 017-872-H

Thornton, Colorado, 80260

Not Yet Recruiting

Site 017-872-H · Contact

Mayo Clinic - Jacksonville

Jacksonville, Florida, 32224

Recruiting

Yan Yan Lou, Site 017-829 · Contact

713-878-8182

The Oncology Institute of Hope and Innovation - Lakeland

Lakeland, Florida, 33812

Recruiting

Kamal Sharma, Site 017-898 · Contact

863-208-6343

Local Institution - Unk076

Miami, Florida, 33136

Active Not Recruiting

Local Institution - Unk055

Orlando, Florida, 32803

Active Not Recruiting

Local Institution - Unk062

Chicago, Illinois, 60612

Active Not Recruiting

University of Chicago

Chicago, Illinois, 60637

Recruiting

Marina Garassino, Site 017-972 · Contact

Local Institution - 017-820J

Fairway, Kansas, 66205

Not Yet Recruiting

Site 017-820J · Contact

Local Institution - 017-820A

Kansas City, Kansas, 66160

Not Yet Recruiting

Site 017-820A · Contact

Local Institution - 017-820B

Kansas City, Kansas, 66160

Not Yet Recruiting

Site 017-820B · Contact

Local Institution - 017-820C

Kansas City, Kansas, 66160

Not Yet Recruiting

Site 017-820C · Contact

Local Institution - 017-820H

Kansas City, Kansas, 66160

Not Yet Recruiting

Site 017-820H · Contact

Local Institution - 017-820I

Overland Park, Kansas, 66210

Not Yet Recruiting

Site 017-820I · Contact

University of Kansas Cancer Center - Westwood/Richard and Annette Bloch Cancer Care Pavilion

Westwood, Kansas, 66205

Recruiting

Jun Zhang, Site 017-820 · Contact

646-407-2086

Local Institution - 017-965

Lexington, Kentucky, 40503

Withdrawn

Local Institution - Unk009

Baltimore, Maryland, 21201

Active Not Recruiting

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115

Recruiting

Daniel Costa, Site 017-388 · Contact

617-667-9236

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Recruiting

Pasi Janne, Site 017-808 · Contact

617-632-6036

Local Institution - Unk039

Burlington, Massachusetts, 01803

Active Not Recruiting

Local Institution - Unk069

Detroit, Michigan, 48201

Active Not Recruiting

Local Institution - Unk018

Lansing, Michigan, 488912

Active Not Recruiting

Henry Ford Medical Center - Columbus

Novi, Michigan, 48377

Recruiting

Shirish Gadgeel, Site 017-811 · Contact

313-399-0508

Local Institution - 017-838B

Minneapolis, Minnesota, 55404

Not Yet Recruiting

Site 017-838B · Contact

Local Institution - 017-838C

Minneapolis, Minnesota, 55404

Not Yet Recruiting

Site 017-838C · Contact

Mayo Clinic - Rochester

Rochester, Minnesota, 55905

Recruiting

Konstantinos Leventakos, Site 017-830 · Contact

507-284-2511

Metro-Minnesota Community Oncology Research Consortium (MMCORC)

Saint Louis Park, Minnesota, 55416

Recruiting

Yan Ji, Site 017-838 · Contact

952-993-3252

Local Institution - 017-838A

Saint Louis Park, Minnesota, 55426-5000

Not Yet Recruiting

Site 017-838A · Contact

Local Institution - 017-820F

Kansas City, Missouri, 64116

Not Yet Recruiting

Site 017-820F · Contact

Local Institution - 017-820E

Kansas City, Missouri, 64154

Not Yet Recruiting

Site 017-820E · Contact

Local Institution - 017-820D

Lee's Summit, Missouri, 64064

Not Yet Recruiting

Site 017-820D · Contact

Local Institution - 017-820G

North Kansas City, Missouri, 64116

Not Yet Recruiting

Site 017-820G · Contact

Local Institution - Unk008

Osage Beach, Missouri, 65065

Active Not Recruiting

Local Institution - Unk058

Springfield, Missouri, 65807

Active Not Recruiting

Local Institution - 017-080

Babylon, New York, 11702

Not Yet Recruiting

Site 017-080 · Contact

Local Institution - 017-088

Brooklyn, New York, 11210

Not Yet Recruiting

Site 017-088 · Contact

Hematology-Oncology Associates of Central New York - Brittonfield - East Syracuse

East Syracuse, New York, 13057

Recruiting

Ajeet Gajra, Site 017-587 · Contact

315-425-3456

Local Institution - 017-087

New Hyde Park, New York, 11042

Not Yet Recruiting

Site 017-087 · Contact

Local Institution - 017-085

New York, New York, 10028

Not Yet Recruiting

Site 017-085 · Contact

Local Institution - 017-082

Patchogue, New York, 11772

Not Yet Recruiting

Site 017-082 · Contact

Local Institution - 017-086

Port Jefferson, New York, 11776

Not Yet Recruiting

Site 017-086 · Contact

Local Institution - 017-081

Port Jefferson Station, New York, 11776

Not Yet Recruiting

Site 017-081 · Contact

New York Cancer & Blood Specialists - Cancer Center - Research Headquarters

Port Jefferson Station, New York, 11776

Recruiting

Richard Zuniga, Site 017-535 · Contact

631-675-5075

Local Institution - 017-084

Riverhead, New York, 11901

Not Yet Recruiting

Site 017-084 · Contact

Local Institution - 017-945

The Bronx, New York, 10467

Withdrawn

Local Institution - 017-083

The Bronx, New York, 10469

Not Yet Recruiting

Site 017-083 · Contact

Cleveland Clinic Main Campus

Cleveland, Ohio, 44195

Recruiting

Nathan Pennell, Site 017-818 · Contact

216-445-9282

Local Institution - 017-836

Kettering, Ohio, 45429

Withdrawn

Local Institution - 017-916

Memphis, Tennessee, 38104

Withdrawn

Texas Oncology - Dallas Fort Worth (DFW) - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246

Recruiting

Kartik Konduri, Site 017-879 · Contact

214-370-1000

Local Institution - Unk056

Dallas, Texas, 75390

Active Not Recruiting

Local Institution - 017-848

Houston, Texas, 77030

Withdrawn

Local Institution - 017-999

Irving, Texas, 75063

Not Yet Recruiting

Site 017-999 · Contact

USOR - Texas Oncology Northeast Texas - Longview Cancer Center

Longview, Texas, 75601

Recruiting

Donald Richards, Site 017-878 · Contact

903-579-9800

Local Institution - 017-878-B

Palestine, Texas, 75801

Not Yet Recruiting

Site 017-878-B · Contact

Local Institution - 017-878-C

Paris, Texas, 75460

Not Yet Recruiting

Site 017-878-C · Contact

Local Institution - 017-878-A

Tyler, Texas, 75702

Not Yet Recruiting

Site 017-878-A · Contact

Local Institution - Unk010

Salt Lake City, Utah, 84106

Active Not Recruiting

Local Institution - 017-814-A

Arlington, Virginia, 22205

Not Yet Recruiting

Site 017-814-A · Contact

Local Institution - Unk066

Fairfax, Virginia, 22031

Active Not Recruiting

Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia, 22031

Recruiting

Alexander Spira, Site 017-814 · Contact

703-280-5390

Local Institution - 017-814-B

Gainesville, Virginia, 20155

Not Yet Recruiting

Site 017-814-B · Contact

Local Institution - 017-814-C

Reston, Virginia, 20190

Not Yet Recruiting

Site 017-814-C · Contact

PeaceHealth St. Joseph Medical Center

Bellingham, Washington, 98225

Recruiting

Drew Murray, Site 017-909 · Contact

360-788-8222

Local Institution - Unk036

Huntington, West Virginia, 25705

Active Not Recruiting