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.
Phase 2: Histologically confirmed diagnosis of unresectable or metastatic NSCLC with KRAS G12C mutation and any PD-L1 TPS
Phase 3: Histologically confirmed diagnosis of unresectable or metastatic squamous or nonsquamous NSCLC with KRAS G12C mutation and PD-L1 TPS>=50%
Phase 3: Presence of measurable disease per RECIST1.1
No evidence of brain metastases
Phase 2 and Phase 3: Prior systemic treatment for locally advanced or metastatic NSCLC including chemotherapy, immune checkpoint inhibitor therapy, or a therapy targeting KRAS G12C mutation (e.g., AMG 510).
Phase 2: Active brain metastases
Any untreated brain lesions > 2.0 cm in size
Any brainstem lesions
Parallel
Adagrasib
DrugAdagrasib 400 mg twice daily (BID) in combination with pembrolizumab (Cohort 1a)
Adagrasib
DrugAdagrasib 600 mg BID monotherapy (Cohort 1b)
Adagrasib
Drugadagrasib 400 mg BID in combination with pembrolizumab
Adagrasib
DrugAdagrasib 400 mg BID + pembrolizumab 200 mg every Q3W
Pembrolizumab
DrugPembrolizumab 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)
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
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.
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.
Phase 2: Progression Free Survival
Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Phase 2: To evaluate secondary efficacy endpoints using the study treatment in selected populations
1-Year Survival rate
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