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RecruitingLast updated: 10 July 2026

KRYSTAL-7: Targeted therapy (MRTX849) alone, or in combination with immunotherapy for people with advanced or metastatic non-small cell lung cancer with KRAS G12C mutationA Phase 2 Trial of MRTX849 Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination With Pembrolizumab Versus Pembrolizumab Plus Chemotherapy in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

Trial purpose

Medical clipboardCancer treatment

Tumor type

Lung Cancers Lung cancer

Age

People18+

Trial acronym

KRYSTAL-7

Clinical summary

Summary

This clinical trial is testing new treatment options for people with advanced non-small cell lung cancer (NSCLC) who have a specific gene change called KRAS G12C.

The study is looking at how well these treatments work, how safe they are, and how well people tolerate them. It focuses on people who are starting treatment for the first time for their advanced cancer.

To be eligible for this study, you must not have received prior systemic treatment for locally advanced or metastatic NSCLC, including chemotherapy, immune checkpoint inhibitor therapy, or a therapy targeting KRAS G12C mutation.

What treatments are being studied?
The trial involves two medicines:

  • Adagrasib (also called MRTX849) - a targeted therapy tablet that blocks the KRAS G12C mutation, which helps cancer grow.
  • Pembrolizumab (Keytruda®) - an immunotherapy drug given by IV infusion that helps your immune system recognise and attack cancer.

The study has two parts: Phase 2 and Phase 3.

Phase 2
This part is testing adagrasib on its own, and adagrasib combined with pembrolizumab. Participants will be placed into groups based on a tumour test called PD-L1.

  • There will be two groups of participants with a PD-L1 score less than 1%. These participants will be randomly assigned (by chance) to receive either:
    • adagrasib alone, or 
    • adagrasib in combination with pembrolizumab
  • A third group includes participants with a PD-L1 score of 1% or higher. These participants will receive adagrasib together with pembrolizumab. 

Phase 3
This part compares adagrasib + pembrolizumab with pembrolizumab alone. The aim is to find out whether adding adagrasib to pembrolizumab improves treatment outcomes. Participants in this part will have a PD-L1 score of 50% or higher.

Participants will be randomly allocated (by chance) to receive either adagrasib + pembrolizumab, or pembrolizumab alone.

 

 

 

Conditions

This trial is treating people with advanced or metastatic non-small cell lung cancer with KRAS G12C mutation

Eligibility

Inclusion

  • 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 measurable disease per RECIST1.1
  • 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

  • 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 > 2.0 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

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • Your cancer has not spread to other parts of the body, but it is not possible to perform surgery to remove it (unresectable).

Exclusion

  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

Recruiting hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

Trial sponsor

Mirati Therapeutics Inc.

Scientific Title

A Phase 2 Trial of MRTX849 Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination With Pembrolizumab Versus Pembrolizumab Plus Chemotherapy in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

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