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Treatment for advanced lung cancer with KRAS G12C mutation

A Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

Phase2; Phase3 Interventional Mirati Therapeutics Inc. · NCT04613596

This study is testing a new treatment called adagrasib, alone and with another drug called pembrolizumab, to see if it helps people with advanced lung cancer that has a specific mutation.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment806 (estimated)
Ages18 Years and up
SexAll
SponsorMirati Therapeutics Inc. Industry-sponsored
Drugs / interventionschemotherapy, Radiation, prednisone, pembrolizumab
Locations764 sites (Goodyear, Arizona and 763 other locations)
Trial IDNCT04613596 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of adagrasib, both as a standalone treatment and in combination with pembrolizumab, for patients with advanced non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation. The study consists of two phases: Phase 2 assesses the treatment in patients with varying PD-L1 TPS scores, while Phase 3 compares the combination therapy against pembrolizumab alone in patients with high PD-L1 expression. The trial aims to determine the effectiveness of these treatments as first-line options for patients with unresectable or metastatic NSCLC.

Who should consider this trial

Good fit: Ideal candidates include patients with unresectable or metastatic NSCLC with a confirmed KRAS G12C mutation and specific PD-L1 TPS scores.

Not a fit: Patients who have previously received systemic treatment for locally advanced or metastatic NSCLC or those with active brain metastases may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could provide a new effective treatment option for patients with advanced lung cancer that has a specific genetic mutation.

How similar studies have performed: Other studies targeting KRAS mutations have shown promise, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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 evaluable or measurable disease per RECIST
* Phase 3: CNS Inclusion - Based on screening brain imaging, patients must have one of the following:

  1. No evidence of brain metastases
  2. Untreated brain metastases not needing immediate local therapy
  3. Previously treated brain metastases not needing immediate local therapy

Exclusion Criteria:

* 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
* Phase 3: Patients with known central nervous system (CNS) lesions must not have any of the following:

  1. Any untreated brain lesions \> 1.0 cm in size
  2. Any brainstem lesions
  3. Ongoing use of systemic corticosteroids for control of symptoms of brain lesions at a total daily dose of \> 10 mg of prednisone (or equivalent) prior to randomization.
  4. Have poorly controlled (\> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain lesions notwithstanding CNS-directed therapy
* Phase 3: Radiation to the lung \> 30 Gy within 6 months prior to the first dose of study treatment

Where this trial is running

Goodyear, Arizona and 763 other locations

+714 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Non-Small Cell Lung CancerMetastatic Non-Small Cell Lung CancerKRAS G12CNon-small cell lung cancerNSCLCAdagrasibKrazatiTPS
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.