A Phase 2/3 interventional study of Adagrasib and Adagrasib in Advanced Non-Small Cell Lung Cancer and Metastatic Non-Small Cell Lung Cancer, sponsored by Mirati Therapeutics Inc.. Recruiting at 770 sites in 47 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-16.
Sponsored by Mirati Therapeutics Inc. · Phase 2/3, Interventional, and Treatment
The Phase 2 portion of this study evaluates the efficacy and safety of MRTX849 monotherapy and in combination with pembrolizumab in cohorts of patients with advanced NSCLC with KRAS G12C mutation and any PD-L1 TPS and who are candidates for first-line treatment.
The Phase 3 portion of the study compares the efficacy of adagrasib in combination with pembrolizumab versus pembrolizumab in patients with unresectable, locally advanced or metastatic squamous or nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS >=50% and who are candidates for first line treatment.
The Phase 2 portion of this study will evaluate the efficacy and safety of MRTX849 as monotherapy and in combination with pembrolizumab. There will be 3 cohorts of patients, all of whom have KRAS G12C mutation, have advanced or metastatic NSCLC, and are candidates for first-line treatment. 2 cohorts have PD-L1 TPS score \<1% and are randomized to MRTX849 monotherapy or MRTX849 in combination with pembrolizumab. The 3rd cohort has PD-L1 TPS score of 1% or higher and is treated with MRTX849 and pembrolizumab
The Phase 3 portion of the study will randomize patients with squamous or nonsquamous NSCLC with KRAS G12C mutation and TPS >=50% in the first-line setting to adagrasib plus pembrolizumab or pembrolizumab. Primary efficacy objective is to compare efficacy between experimental and comparator arms. Secondary and exploratory objectives include evaluation of secondary efficacy endpoints, safety and tolerability, adagrasib PK, PROs, and correlative genomic biomarkers for the combination regimen in the study population.
MRTX849 is an orally available small molecule inhibitor of KRAS G12C, and Pembrolizumab (KEYTRUDA®) is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Phase 3: CNS Inclusion - Based on screening brain imaging, patients must have one of the following:
Exclusion Criteria:
Phase 3: Patients with known central nervous system (CNS) lesions must not have any of the following:
Cohort 1a: Adagrasib twice daily (BID) in combination with pembrolizumab
Drug: Adagrasib
Cohort 1b: Adagrasib BID monotherapy
Drug: Adagrasib
Cohort 2: Adagrasib BID in combination with pembrolizumab
Drug: Adagrasib
Adagrasib BID in combination with pembrolizumab
Drug: Adagrasib
Pembrolizumab
Drug: Pembrolizumab
Adagrasib 400 mg twice daily (BID) in combination with pembrolizumab (Cohort 1a)
Also known as: Pembrolizumab
Adagrasib 600 mg BID monotherapy (Cohort 1b)
adagrasib 400 mg BID in combination with pembrolizumab
Also known as: Pembrolizumab
Adagrasib 400 mg BID + pembrolizumab 200 mg every Q3W
Also known as: Pemrolizumab
Pembrolizumab 200 mg IV Q3W
Phase 2: To evaluate the efficacy of Adagrasib monotherapy and in combination with pembrolizumab administered to patients having advanced/metastatic NSCLC.
Objective Response Rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Time frame: 22 months
Phase 3: To compare efficacy of Adagrasib in combination with pembrolizumab versus pembrolizumab
Progression Free Survival per RECIST 1.1 by Blinded Independent Central Review (BICR) and Overall Survival
Time frame: 36 months
Phase 2: To characterize the safety and tolerability of study treatments in selected populations
Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities.
Time frame: 22 months
Phase 2: Duration of Response
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.
Time frame: 22 months
Phase 2: Progression Free Survival
Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Time frame: 22 months
Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations
1-Year Survival rate
Time frame: 12 months
Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations
Overall Survival (OS)
Time frame: 22 months
Phase 2: To evaluate the pharmacokinetics (PK) of study treatments by measuring blood plasma MRTX849 and potential metabolite concentrations.
Pharmacokinetics (PK) Blood plasma Adagrasib and potential metabolite concentrations
Time frame: 22 months
Phase 3: To evaluate the safety and tolerability in the study population
Safety characterized by type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and laboratory abnormalities.
Time frame: 36 months
Phase 3: To evaluate health-related quality of life (HRQOL) and lung cancer specific symptoms in the study population
Patient Reported Outcomes to measure quality of life
Time frame: 36 months
Phase 3: Progression Free Survival per RECIST 1.1 by Investigator
Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Time frame: 36 months
Phase 3: Duration of Response (DOR) per RECIST 1.1 by Investigator and BICR
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.
Time frame: 36 months
Phase 3: Objective Response Rate (ORR) per RECIST 1.1 by Investigator and BICR
Defined as the percent of patients documented to have a confirmed CR or PR.
Time frame: 36 months
Showing the first 100 of 770 sites across 47 countries.
Plan to share: Yes — 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
Supporting information: Study protocol, Sap, Csr
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Carcinoma, Non-Small-Cell Lung→
Mirati Therapeutics Inc.