NCT06875310Recruiting
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)
Summary
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
Inclusion criteria
• 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 criteria
• 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.
Contacts
The trial team's contact details are shown on request.
See the official trial record- Status
- Recruiting
- Phase
- Phase 3
- Study type
- Interventional
- Countries
- Switzerland, France, Germany, Italy, Austria, United States, Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Greece, Hong Kong, Hungary, India, Ireland, Israel, Japan, Mexico, Netherlands, Poland, Portugal, Romania, Saudi Arabia, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom
- Sponsor
- Mirati Therapeutics Inc.(Industry)
- Protocol no.
- CA239-0004
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Drug
Treatments studied
- Adagrasib
- Pembrolizumab
- Carboplatin
- Pemetrexed
- Placebo
- Cisplatin
Locations · 303
- Münsterlingen, SwitzerlandKantonsspital Münsterlingen - Spital Thurgau AGRecruiting at this site
- Caen, FranceCentre François BaclesseRecruiting at this site
- Dijon, FranceCentre Georges François LeclercRecruiting at this site
- Brest, FranceCHRU de BrestRecruiting at this site
- Montpellier, FranceInstitut Régional du Cancer MontpellierRecruiting at this site
- La Tronche, FranceChu Grenoble AlpesRecruiting at this site
- Angers, FranceCentre Hospitalier Universitaire d'AngersRecruiting at this site
- Vandœuvre-lès-Nancy, FranceCentre Hospitalier Régional Universitaire de Nancy - Hôpitaux de BraboisRecruiting at this site
- Marseille, FranceInstitut Paoli-CalmettesRecruiting at this site
- Amiens, FranceCHU d'Amiens-Picardie - Hôpital SudRecruiting at this site
- Villejuif, FranceGustave RoussyRecruiting at this site
- Boulogne-Billancourt, FranceHôpital Ambroise ParéRecruiting at this site
- Clermont-Ferrand, FranceChu Gabriel MontpiedRecruiting at this site
- Limoges, FranceCentre Hospitalier Universitaire de Limoges - Hôpital DupuytrenRecruiting at this site
- Marseille, FranceAssistance Publique Hôpitaux de Marseille - Hôpital NordRecruiting at this site
- Paris, FranceHopitaux Universitaires Paris Centre-Hopital CochinRecruiting at this site
- Saint-Herblain, FranceHôpital Nord Guillaume-et-René-Laennec / CHU de NantesRecruiting at this site
- Esslingen am Neckar, GermanyKlinikum EsslingenRecruiting at this site
- Ulm, GermanyBundeswehrkrankenhaus UlmRecruiting at this site
- München, GermanyKlinikum der Ludwig-Maximilians-Universitaet MuenchenRecruiting at this site
- Frankfurt am Main, GermanyCentrum für Hämatologie und Onkologie BethanienRecruiting at this site
- Giessen, GermanyUKGM Gießen/MarburgRecruiting at this site
- Hanover, GermanyPraxis Onkologie am RaschplatzRecruiting at this site
- Oldenburg, GermanyPius Hospital OldenburgRecruiting at this site
- Cologne, GermanyKlinikum Köln-MerheimRecruiting at this site
- Herne, GermanyEvangelisches Krankenhaus Herne - EickelRecruiting at this site
- Halle, GermanyUniversitätsklinikum HalleRecruiting at this site
- Flensburg, GermanyMalteser Krankenhaus St. Franziskus-HospitalRecruiting at this site
- Gera, GermanySRH Wald-Klinikum Gera GmbHRecruiting at this site
- Jena, GermanyUniversitätsklinikum JenaRecruiting at this site
In total, worldwide, 303 of the 317 sites listed in the registry are recruiting; the other 14 are not currently recruiting.
Site status per the ClinicalTrials.gov registry (last update posted: October 27, 2026).
This status may have changed and says nothing about your eligibility: before taking any step, check with your oncologist or the site.
+ 273 more locations
Other identifiers
- 2024-515698-85 · other identifier
- U1111-1309-5596 · other identifier
- CA2390004 · other identifier
Other versions
These results are indicative and do not replace medical advice — discuss them with your doctor.