A Study of Adagrasib Plus Pembrolizumab Plus Chemotherapy vs. Placebo Plus Pembrolizumab Plus Chemotherapy in Participants With Previously Untreated Non-squamous Non-small Cell Lung Cancer With KRAS G12C Mutation (KRYSTAL-4)

Recruiting now · Phase 3 · Has a placebo group

Conditions studied: Carcinoma, Non-Small-Cell Lung

In brief

This is a trial to evaluate the efficacy, safety, and tolerability of adagrasib plus pembrolizumab plus platinum-doublet chemotherapy versus placebo plus pembrolizumab plus platinum-doublet chemotherapy in participants with previously untreated, locally advanced or metastatic NSCLC with KRAS G12C mutation

Key facts

Study ID

NCT06875310

Run by

Mirati Therapeutics Inc.

People needed

630

Starts

2025-04-24

Expected to finish

2032-04-30

Last updated by the study team

2026-07-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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.

Where it is running

• Texas Oncology - San Antonio — San Antonio, Texas, United States (enrolling)
• Hospital Italiano de Buenos Aires — ABB, Buenos Aires F.D., Argentina (enrolling)
• Louisiana State University Health Sciences Shreveport — Shreveport, Louisiana, United States (enrolling)
• Texas Oncology Sammons Cancer Center — Dallas, Texas, United States (enrolling)
• IDIM - Instituto de Investigaciones Metabólicas — Ciudad de Buenos Aires, Buenos Aires, Argentina (enrolling)
• Hospital Universitario Austral — Pilar, Buenos Aires, Argentina (enrolling)
• Saint Elizabeth Medical Center Edgewood — Edgewood, Kentucky, United States (enrolling)
• Owensboro Medical Health System — Owensboro, Kentucky, United States (enrolling)
• Maryland Oncology Hematology - Columbia — Columbia, Maryland, United States (enrolling)
• SCRI Oncology Partners — Nashville, Tennessee, United States (enrolling)
• Instituto Alexander Fleming — Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina (enrolling)
• Cancer Care Centers of Brevard, Inc. — Palm Bay, Florida, United States (enrolling)
• Florida Clinical Trials Group. — Plantation, Florida, United States (enrolling)
• Medical Oncology Hematology Consultants, PA — Newark, Delaware, United States (enrolling)
• Florida Clinical Trials Group. — Tamarac, Florida, United States (enrolling)
• Mercy Medical Center — Cedar Rapids, Iowa, United States (enrolling)
• Cancer Specialists of North Florida — Jacksonville, Florida, United States (enrolling)
• Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital — Marietta, Georgia, United States (enrolling)
• Illinois Cancer Specialists — Arlington Heights, Illinois, United States (enrolling)
• Helios Clinical Research — Long Beach, California, United States (enrolling)
• Ellis Hospital — Schenectady, New York, United States (enrolling)
• WellSpan Oncology Research — York, Pennsylvania, United States (enrolling)
• Mid Florida Hematology and Oncology Center — Orange City, Florida, United States (enrolling)
• Texas Oncology - Northeast Texas — Tyler, Texas, United States (enrolling)
• Clinica Adventista Belgrano — CABA, Buenos Aires F.D., Argentina (enrolling)

Full record on ClinicalTrials.gov

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