KEAPSAKE

A Phase 2 Randomized, Multicenter, Double-Blind Study of the Glutaminase Inhibitor Telaglenastat With Pembrolizumab and Chemotherapy Versus Placebo With Pembrolizumab and Chemotherapy in First-Line, Metastatic KEAP1/NRF2-Mutated, Nonsquamous, Non-Small Cell Lung Cancer (NSCLC)

Objective

The study objectives and endpoints were designed to determine the benefit of telaglenastat in combination with pembrolizumab plus chemotherapy compared with placebo in combination with pembrolizumab plus chemotherapy as first-line treatment of patients with metastatic KEAP1- or NRF2-mutated nonsquamous Stage IV NSCLC.

Study Arms

  • Experimental: Telaglenastat with Pembrolizumab and Chemotherapy
  • Placebo Comparator: Placebo with Pembrolizumab and Chemotherapy

Eligibility

  • Histologically or cytologically documented nonsquamous NSCLC
  • Stage IV (M1a-c, AJCC 8th Edition) disease not previously treated with systemic therapy for metastatic NSCLC
    • Patients who received adjuvant or neoadjuvant therapy (with or without immunotherapy) for localized NSCLC are eligible if all adjuvant/neoadjuvant therapy (including immunotherapy) was completed at least 6 months prior to the development of metastatic disease.
  • No known actionable mutation in EGFR, ALK, ROS1, BRAF, NTRK or other known actionable mutation for which there is approved therapy.
  • Measurable disease per RECIST 1.1.
  • Life expectancy of at least 3 months.
  • Mutation in KEAP1 or NRF2 documented by NGS from a CAP-accredited and/or CLIA-certified laboratory and STK11/LKB1 mutation status is known for the purpose of stratification.
  • Adequate hepatic, renal, cardiac and hematologic function.
  • Willingness to use adequate contraception as defined in the study protocol

NCT ID

NCT04265534