Combination Therapies With Adagrasib in Patients With Advanced NSCLC With KRAS G12C Mutation

Phase 2

Recruiting

• Conditions: Advanced NSCLC; Metastatic Lung Cancer
• Interventions: Drug: Adagrasib oral dose of 400 mg twice daily tablets; Combination Product: Pembrolizumab; Combination Product: Cisplatin/Carboplatin

• Registration Number: NCT05609578
• Lead Sponsor: Mirati Therapeutics Inc.

Brief 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-01
• Study First Submitted QC: 2022-11-01
• Study First Posted: 2022-11-08
• Study Start: 2022-11-30
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-09
• Last Update Posted: 2025-05-11
• Primary Completion: 2026-06-01
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 90

Inclusion Criteria

Not provided

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort C	Adagrasib oral dose of 400 mg twice daily tablets	Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles
Cohort E	Adagrasib oral dose of 400 mg twice daily tablets	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)
Cohort E	Cisplatin/Carboplatin	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)
Cohort C	Cisplatin/Carboplatin	Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles
Cohort A: PD-L1 TPS≥ 1% (Closed)	Adagrasib oral dose of 400 mg twice daily tablets	Adagrasib 400 mg BID for 2 cycles followed by adagrasib 400 mg BID + pembrolizumab 200 mg every 3 weeks (Q3W) up to 35 cycles
Cohort E	Pembrolizumab	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)
Cohort C	Pembrolizumab	Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR)	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.
Overall Survival (OS)	30 months	Defined as time from date of first study treatment to date of death due to any cause
Population pharmacokinetic (PK) Model Derived AUC at Steady State (AUCtau,ss).	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.
Adverse Events	30 months	Defined as number of patients with treatment emergent AEs
Progression-free Survival (PFS)	30 months	Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Cohorts C and E: DLTs during SLI (Safety Lead In)	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.

Trial Locations

Locations (166)

Local Institution - Unk025; 🇺🇸 Anchorage, Alaska, United States

Local Institution - 017-591; 🇺🇸 Glendale, Arizona, United States

Local Institution - 017-821; 🇺🇸 Phoenix, Arizona, United States

Local Institution - Unk047; 🇺🇸 Anaheim, California, United States

Local Institution - 017-936C; 🇺🇸 Fountain Valley, California, United States

MemorialCare - Orange Coast Medical Center; 🇺🇸 Fountain Valley, California, United States

Providence Medical Foundation - Virginia K. Crosson Cancer Center - Fullerton; 🇺🇸 Fullerton, California, United States

Local Institution - Unk004; 🇺🇸 Loma Linda, California, United States

Local Institution - 017-961; 🇺🇸 Los Angeles, California, United States

UCSF Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

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