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)

Sponsor: Mirati Therapeutics Inc.

Sponsor score: 40

ClinicalTrials ID:NCT06875310

This trial assesses the efficacy, safety, and tolerability of adagrasib with pembrolizumab and chemotherapy in untreated, advanced NSCLC with KRAS G12C mutation. Eligible participants have confirmed non-squamous NSCLC, measurable disease, and no prior systemic therapy. Interventions include adagrasib, pembrolizumab, carboplatin, pemetrexed, placebo, and cisplatin.

Patient Parameters

Program Overview

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

Eligibility Criteria

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.

Exclusion Criteria

  • Participants with an active, known, prior documented, or suspected autoimmune or inflammatory disease.
  • Uncontrolled or significant cardiovascular conditions within 6 months prior to enrollment.
  • 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.

Locations

FACILITYZIPCITYSTATE
Local Institution - 034735294-3300BirminghamAlabama
Local Institution - 058192835FullertonCalifornia
Local Institution - 020290805Long BeachCalifornia
Local Institution - 064392663Newport BeachCalifornia
Local Institution - 066692868OrangeCalifornia
Local Institution - 062393105Santa BarbaraCalifornia
Local Institution - 044280206DenverColorado
Local Institution - 065132610GainesvilleFlorida
Local Institution - 062132901Palm BayFlorida
Local Institution - 037733321TamaracFlorida

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