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

Mirati Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Advanced NSCLC; Metastatic Lung Cancer

Treatments: Combination Product: Cisplatin/Carboplatin; Combination Product: Chemotherapy: Pemetrexed; Combination Product: Pembrolizumab; Drug: Adagrasib oral dose of 400 mg twice daily tablets

Study type: Interventional

Funder types: Industry

Identifiers

NCT05609578

849-017

CA239-0010

Details and patient eligibility

About

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

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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90 participants in 3 patient groups

Cohort A: PD-L1 TPS≥ 1% (Closed)

Experimental group

Description:

Adagrasib 400 mg BID for 2 cycles followed by adagrasib 400 mg BID + pembrolizumab 200 mg every 3 weeks (Q3W) up to 35 cycles

Treatment:

Drug: Adagrasib oral dose of 400 mg twice daily tablets

Cohort C

Experimental group

Description:

Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles

Treatment:

Drug: Adagrasib oral dose of 400 mg twice daily tablets

Combination Product: Pembrolizumab

Combination Product: Chemotherapy: Pemetrexed

Combination Product: Cisplatin/Carboplatin

Cohort E

Experimental group

Description:

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)

Treatment:

Drug: Adagrasib oral dose of 400 mg twice daily tablets

Combination Product: Pembrolizumab

Combination Product: Chemotherapy: Pemetrexed

Combination Product: Cisplatin/Carboplatin