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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)

NCT 06875310

Brief 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

Intervention / Treatment 

  • Drug: Adagrasib
  • Drug: Pembrolizumab
  • Drug: Carboplatin
  • Drug: Pemetrexed
  • Drug: Placebo
  • Drug: Cisplatin

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor tissue 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.

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