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RecruitingLast updated: 14 May 2026

KRYSTAL-4: This study is recruiting people with advanced non-small cell lung cancer with a KRAS G12C mutation to evaluate a treatment with targeted therapy, immunotherapy and chemotherapyA Randomized, Double-Blind, Phase 3 Trial of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated, Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

Trial purpose

Medical clipboardCancer treatment

Tumor type

Lung Cancers Lung cancer

Age

People18+

Trial acronym

KRYSTAL-4

Clinical summary

Summary

This study is recruiting people with non-squamous non-small cell lung cancer (NSCLC) with KRAS G12C mutation that is locally advanced or metastatic, who have not received treatment for their advanced disease and are not eligible for definitive therapy.

Eligible participants will be randomly allocated (by chance) to one of two treatment groups.

In the Experimental Group, participants will receive Adagrasib targeted therapy, plus Pembrolizumab immunotherapy and platinum-doublet chemotherapy.

In the Placebo Comparator Group, participants will receive a placebo plus Pembrolizumab immunotherapy and platinum-doublet chemotherapy.

 

Conditions

This trial is treating people with non-squamous, non-small cell lung cancer with KRAS G12C mutation who have not had prior treatment for their advanced disease

Eligibility

Inclusion

  • Histologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor sample and/or circulating tumor deoxyribonucleic acid (ctDNA).
  • Locally advanced or metastatic disease.
  • Measurable disease via computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST v1.1 criteria of at least 1 lesion.
  • No prior systemic anti-cancer therapy given for advanced or metastatic disease.
  • Not a candidate for definitive therapy (eg, chemoradiation or complete surgical resection).
  • Participants with brain metastases are eligible for enrollment, including those with untreated brain metastases. Brain metastases must be asymptomatic and not in need of immediate local therapy. Any untreated brain metastases must be ≤ 20 mm in diameter.
  • Any PD-L1 expression (0 to 100%) as determined by VENTANA PD-L1 (SP263) assay, Agilent PD-L1 IHC 22C3 pharmDx, or Agilent PD-L1 IHC 28-8 pharmDx.

Exclusion

  • Participants with an active autoimmune or inflammatory disease requiring systemic treatment within 2 years.
  • Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment that are ongoing or with risk of recurrence.
  • Inadequate bone marrow or liver function or electrocardiogram (ECG) abnormalities.
  • Ongoing treatment with concomitant medication known to cause prolonged QTc interval and that cannot be switched to alternative treatment prior to study entry.
  • Treatment targeting KRAS G12C mutation (eg, sotorasib, adagrasib) in any setting.
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration.
  • Other protocol-defined Inclusion/Exclusion criteria apply.

Inclusion

  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).

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 Randomized, Double-Blind, Phase 3 Trial of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated, Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

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