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NCT Number: NCT05609578

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

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

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Advanced NSCLC Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Metastatic Lung Cancer Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Local Institution - 017-689, Angers, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Adagrasib oral dose of 400 mg twice daily tablets

Drug

oral dose of 400 mg twice daily tablets

Pembrolizumab

Combination Product

IV infusion once every 3 weeks

Chemotherapy: Pemetrexed

Combination Product

IV infusion once every 3 weeks

Cisplatin/Carboplatin

Combination Product

IV infusion once every 3 weeks

Primary outcomes

  1. Objective Response Rate (ORR) for Cohort A and E

    Time frame: 30 months

    Defined as the percent of patients documented to have a confirmed CR or PR

  2. Progression-free Survival (PFS) at six months for Cohort C

    Time frame: 30 months

    PFS is defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.

Secondary outcomes

  1. Adverse Events

    Time frame: 30 months

    Defined as number of patients with treatment emergent AEs

  2. Duration of Response (DOR)

    Time frame: 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.

  3. Overall Survival (OS)

    Time frame: 30 months

    Defined as time from date of first study treatment to date of death due to any cause

  4. Progression-free Survival (PFS)

    Time frame: 30 months

    Defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.

  5. Population pharmacokinetic (PK) Model Derived AUC at Steady State (AUCtau,ss).

    Time frame: 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.

  6. Cohorts C and E: DLTs during SLI (Safety Lead In)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Mirati Therapeutics Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2022
Primary completion
2026
Study completion
2026
First posted
Nov 8, 2022
Registry last updated
Jun 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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