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

Stopped early · Phase 2 · Has a placebo group

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT04265534

Run by

Calithera Biosciences, Inc

People needed

40

Starts

2020-07-24

Expected to finish

2022-02-09

Last updated by the study team

2022-09-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically or cytologically documented non-squamous NSCLC
• Stage IV (M1a-c, AJCC 8th Edition, Amin 2017) disease not previously treated with systemic therapy for metastatic NSCLC
• a. Patients who received adjuvant or neo-adjuvant therapy (with or without immunotherapy) for localized NSCLC are eligible if all adjuvant/neo-adjuvant 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 in the first-line lung cancer setting
• Must have at least one radiographically measurable lesion per RECIST v1.1 defined as a lesion that is ≥ 10 mm in longest diameter or lymph node that is ≥ 15 mm in short axis imaged by computed tomography (CT) scan or magnetic resonance imaging (MRI)
• a. Target lesions situated in a previously irradiated area may be considered measurable if progression has been demonstrated subsequent to radiation therapy
• Age ≥ 18 years on the day of signing informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Estimated life expectancy of at least 3 months
• Recovery to baseline or ≤ grade 1 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to the prior treatment, unless after discussion with the medical monitor, the AE(s) are deemed clinically non-significant and/or stable on supportive therapy
• Has sponsor-approved eligible mutation in KEAP1 or NRF2 documented by NGS from a CAP-accredited and/or CLIA-certified laboratory (study-provided NGS or other NGS) and STK11 mutation status is known for the purpose of stratification.
• Adequate organ function laboratory findings (defined per protocol)
• Reproductive status:
• a. A female patient of childbearing potential must: i. Have a negative serum pregnancy test within 7 days prior to randomization ii. Agree to use methods of contraception outlined in Section 8.1.2 during the study through 120 days following the last dose of telaglenastat or pembrolizumab, or through 180 days following the last dose of chemotherapeutic drugs iii. Postmenopausal females (no menses for > 1 year without an alternate medical cause) and surgically sterilized females are exempt from these requirements b. Male patients who are sexually active with heterosexual partners of childbearing potential must agree to contraceptive requirements outlined in Section 8.1.2 and refrain from donating sperm during the study through 120 days following the last dose of telaglenastat or pembrolizumab, or through 180 days following the last dose of chemotherapeutic drugs

You may not qualify if…

• Squamous cell histology and mixed histology tumors with any small-cell/neuroendocrine component (other mixed histology should be reviewed with the medical monitor for eligibility)
• Any other concurrent malignancy requiring local or systemic therapy. Patients with other previously treated malignancy(ies) are allowed if the specific neoplasm, in the opinion of the principal investigator and with the agreement of the medical monitor, is not expected to interfere with study-specific endpoints
• Radiation therapy to the lung > 30 Gy within 6 months prior to randomization
• Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)
• a. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Treatment with chronic systemic steroids greater than 10 mg equivalent of prednisone per day
• Unstable/inadequate cardiac function, defined as the following:
• Myocardial infarction or symptomatic ischemia within 6 months prior to randomization
• Uncontrolled or clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with 1st degree atrioventricular [AV] block or asymptomatic left anterior fascicular block [LAFB]/right bundle branch block [RBBB] are eligible)
• Congestive heart failure (New York Heart Association class III to IV)
• Unable to swallow oral medications
• Known sensitivity to any component of the study treatment (pembrolizumab, carboplatin, pemetrexed, and/or telaglenastat) or previous severe hypersensitivity to another monoclonal antibody (mAb)
• Unable or unwilling to take folic acid or vitamin B12 supplementation (per pemetrexed label)
• Unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) as specified in pemetrexed label
• Interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoid treatment
• Unable or unwilling to discontinue proton pump inhibitor (PPI) use ≥ 5 days prior to randomization
• Patient known to be positive for Human Immunodeficiency Virus (HIV)
• Known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg result. Active Hepatitis C is defined by a known positive Hepatitis C antibody result and known quantitative Hepatitis C virus RNA results greater than the lower limits of detection of the assay. Patients receiving antiviral therapy for Hepatitis B or C also are not eligible
• Any condition including social, psychiatric or medical (including uncontrolled significant concurrent illness) that in the opinion of the Investigator could interfere with treatment or protocol-related procedures
• Regular use of illicit drugs or history (within past year) of substance abuse (including alcohol)
• Patients who are pregnant or lactating
• Major surgery < 3 weeks prior to randomization. In addition, patients with ongoing clinically relevant complications from prior surgery are not eligible and they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
• Any radiation therapy within 2 weeks prior to randomization (with exception of SRS for brain metastases). In addition, patients with ongoing clinically relevant complications from prior radiation therapy, patients requiring corticosteroids to treat radiation toxicity and patients who developed radiation pneumonitis are not eligible.
• Symptomatic ascites or pleural effusion. Patients who are clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) are eligible

Where it is running

• University of South Alabama - Mitchell Cancer Center — Mobile, Alabama, United States
• Yuma Regional Medical Center — Yuma, Arizona, United States
• Compassionate Cancer Care — Fountain Valley, California, United States
• St. Joseph Heritage Healthcare — Fullerton, California, United States
• Loma Linda University Medical Center — Loma Linda, California, United States
• University of Southern California (USC) — Los Angeles, California, United States
• Cedars-Sinai Medical Center — Los Angeles, California, United States
• UCLA — Los Angeles, California, United States
• University of California Irvine, Chao Family Comprehensive Cancer Center — Orange, California, United States
• St. Joseph Heritage Healthcare - Santa Rosa — Santa Rosa, California, United States
• Johns Hopkins Sibley Memorial Hospital — Washington D.C., District of Columbia, United States
• Sibley Memorial Hospital — Washington D.C., District of Columbia, United States
• Boca Raton Regional Hospital Lynn Cancer Institute — Boca Raton, Florida, United States
• Holy Cross Hospital - Bines Cancer Center — Fort Lauderdale, Florida, United States
• Florida Cancer Specialist - South (SCRI) — Fort Myers, Florida, United States
• Memorial Cancer Institute at Memorial Hospital West — Hollywood, Florida, United States
• University of Miami Sylvester Comprehensive Cancer Center — Miami, Florida, United States
• Ocala Oncology Center — Ocala, Florida, United States
• Florida Cancer Specialist - North (SCRI) — St. Petersburg, Florida, United States
• Florida Cancer Specialist - Panhandle (SCRI) — Tallahassee, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• Florida Cancer Specialist - East (SCRI) — West Palm Beach, Florida, United States
• University Cancer and Blood Center — Athens, Georgia, United States
• Piedmont Cancer Institute — Atlanta, Georgia, United States
• University of Alabama at Birmingham — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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