KEAPSAKE: A Study of Telaglenastat (CB-839) With Standard-of-Care Chemoimmunotherapy in 1L KEAP1/NRF2-Mutated, Nonsquamous NSCLC

Summary

This is a Phase 2, randomized, multicenter, double-blind study of the glutaminase inhibitor telaglenastat with standard-of-care pembrolizumab and chemotherapy versus placebo with standard-of-care pembrolizumab and chemotherapy for first line treatment of metastatic disease in patients with KEAP1/NRF2-mutated, stage IV, nonsquamous, non-small cell lung cancer (NSCLC). The study primary endpoints are PFS per RECIST v. 1.1 and safety. KEAP1/NRF2 mutation status (for eligibility) and STK11/LKB1 status (for stratification) will be determined by next generation sequencing. A commercial liquid biopsy (circulating tumor DNA) NGS test will be provided to study participants free of charge.

Conditions

• Non-Small Cell Lung Cancer
• Non-squamous Non-small-cell Lung Cancer
• Non-Squamous Non-Small Cell Neoplasm of Lung
• KEAP1 Gene Mutation
• NRF2 Gene Mutation
• NFE2L2 Gene Mutation

Interventions

DRUG

Telaglenastat

Oral Glutaminase Inhibitor

DRUG

Carboplatin Chemotherapy

IV infusion

DRUG

Pemetrexed Chemotherapy

IV infusion

BIOLOGICAL

Pembrolizumab Immunotherapy

IV infusion

DRUG

Placebo

Oral placebo

DIETARY_SUPPLEMENT

Folic acid 400 -1000 μg

Orally, once daily beginning 7 days prior to the first dose of pemetrexed and continue until 21 days after the last dose of pemetrexed.

DIETARY_SUPPLEMENT

Vitamin B12 1000 μg

Vitamin B12 1000 μg Intramuscular injection one week prior to the first dose of pemetrexed and once every 3 cycles (9 weeks) thereafter. Subsequent vitamin B12 injections may be given the same day as pemetrexed administration.

DRUG

Dexamethasone 4 mg

For prophylaxis, orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.

Sponsors & Collaborators

• Calithera Biosciences, Inc

  lead INDUSTRY

Principal Investigators

• Emil Kuriakose, MD · Calithera Biosciences, Inc

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-07-24

Primary Completion

2021-11-05

Completion

2022-02-09

FDA Drug

Yes

Countries

• United States

Study Locations