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Combining Adagrasib with Pembrolizumab and Chemotherapy for Advanced Lung Cancer

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

PHASE2 · Mirati Therapeutics Inc. · NCT05609578

This study is testing if a new combination of a pill called adagrasib, along with pembrolizumab and chemotherapy, can help people with advanced lung cancer that has a specific genetic mutation feel better and live longer.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment90 (estimated)
Ages18 Years and up
SexAll
SponsorMirati Therapeutics Inc. (industry)
Drugs / interventionspembrolizumab, chemotherapy, Radiation
Locations166 sites (Anchorage, Alaska and 165 other locations)
Trial IDNCT05609578 on ClinicalTrials.gov

What this trial studies

This Phase 2 clinical trial evaluates the effectiveness of adagrasib in combination with pembrolizumab and chemotherapy for patients with advanced non-small cell lung cancer (NSCLC) who have a specific KRAS G12C mutation. The study focuses on patients with untreated, unresectable, or metastatic NSCLC and varying levels of PD-L1 expression. Participants will receive an oral dose of adagrasib along with standard chemotherapy agents, aiming to improve treatment outcomes in this challenging patient population.

Who should consider this trial

Good fit: Ideal candidates include patients with untreated, unresectable or metastatic NSCLC with a confirmed KRAS G12C mutation and specific PD-L1 expression levels.

Not a fit: Patients who have previously received treatment for their NSCLC or those without the KRAS G12C mutation may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new effective treatment option for patients with advanced NSCLC harboring the KRAS G12C mutation.

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

Eligibility criteria

Show full inclusion / 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

Where this trial is running

Anchorage, Alaska and 165 other locations

+116 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 →

Conditions: Advanced NSCLC, Metastatic Lung Cancer, KRAS G12C, NSCLC, Non Small Cell Lung Cancer

Last reviewed 2026-05-15 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.