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

Phase 1

Conditions: Advanced Non-Small Cell Lung Cancer
MedDRA version: 21.1Level: PTClassification code: 10061873Term: Non-small cell lung cancer Class: 100000004864
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2023-503714-77-00

Lead Sponsor: Mirati Therapeutics Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 137

Inclusion Criteria

Histologically confirmed diagnosis of unresectable or metastatic NSCLC with KRAS G12C mutation. a.Cohort A* (closed): squamous or nonsquamous histology b.Cohorts C and E*: nonsquamous histology only

Exclusion Criteria

Prior systemic therapy for locally advanced or metastatic NSCLC, including chemotherapy, immune checkpoint inhibitor therapy (CIT in Cohorts A and E only), any therapy targeting KRAS G12C mutation (eg, sotorasib) , or received maintenance therapy, eg, pembrolizumab and/or pemetrexed following completion 4-6 cycles of a platinum-based regimen administered in the first-line setting (Cohort C only), Radiation to the lung > 30 Gy within 6 months prior to first dose of study treatment., Active brain metastases.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Evaluate the efficacy of adagrasib in combination with pembrolizumab and chemotherapy in the first-line setting for advanced NSCLC patients.;Secondary Objective: Characterize the safety and tolerability of the combination regimen in the selected population., Characterize the pharmacokinetics (PK) of adagrasib, Evaluate secondary efficacy endpoints using the combination regimen in the selected population.;Primary end point(s): Cohorts A and E: Objective response rate (ORR), as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)., Cohort C: PFS at 6 months (PFS6)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Cohorts C and E: Dose-limiting toxicities (DLTs) during safety lead-in (SLI);Secondary end point(s):Safety characterized by type, incidence, severity, timing, seriousness, and relationship to study treatment of adverse events (AEs) and laboratory abnormalities;Secondary end point(s):Population PK parameters of adagrasib;Secondary end point(s):Secondary efficacy endpoints: Duration of response (DOR);Secondary end point(s):Secondary efficacy endpoints: PFS;Secondary end point(s):Secondary efficacy endpoints: Overall survival (OS)