Study Stopped
Lack of Clinical Benefit
KEAPSAKE: A Study of Telaglenastat (CB-839) With Standard-of-Care Chemoimmunotherapy in 1L KEAP1/NRF2-Mutated, Nonsquamous NSCLC
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)
1 other identifier
interventional
40
1 country
102
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2 nonsmall-cell-lung-cancer
Started Jul 2020
Shorter than P25 for phase_2 nonsmall-cell-lung-cancer
102 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 7, 2020
CompletedFirst Posted
Study publicly available on registry
February 11, 2020
CompletedStudy Start
First participant enrolled
July 24, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 5, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
February 9, 2022
CompletedSeptember 21, 2022
September 1, 2022
1.3 years
February 7, 2020
September 15, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Progression-Free Survival (PFS), Assessed by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Duration of investigator-determined PFS per RECIST v1.1 in the intent-to-treat (ITT) population
Up to 24 months
Safety and Tolerability of Telaglenastat Plus Standard-of-Care Pembrolizumab and Chemotherapy Assessed by Type, Incidence, Severity, Seriousness, and Study Drug Relatedness of Adverse Events per CTCAE v5.0
Up to 55 months
Recommended Phase 2 Dose of Telaglenastat in Combination with Standard-of-Care Pembrolizumab and Chemotherapy Assessed by Incidence and Nature of Protocol Defined Dose-Limiting Toxicities (DLTs) During the Safety Run-in Period
Up to 6 months
Secondary Outcomes (7)
Objective Response Rate (ORR) for Patients Treated with Telaglenastat plus Standard-of-Care Pembrolizumab and Chemotherapy versus Placebo plus Standard-of-Care Pembrolizumab and Chemotherapy
Up to 24 months
Duration of Response (DOR) for Patients Treated with Telaglenastat plus Standard-of-Care Pembrolizumab and Chemotherapy versus Placebo plus Standard-of-Care Pembrolizumab and Chemotherapy
Up to 24 months
Overall Survival
Up to 55 months
PFS in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway
Up to 24 months
ORR in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway
Up to 24 months
- +2 more secondary outcomes
Study Arms (2)
Telaglenastat with Pembrolizumab and Chemotherapy
EXPERIMENTALThe glutaminase inhibitor telaglenastat will be administered orally, twice daily with food, every day in combination with standard-of-care pembrolizumab plus chemotherapy by intravenous (IV) infusion every 3 weeks.
Placebo with Pembrolizumab and Chemotherapy
PLACEBO COMPARATORPlacebo will be administered orally twice daily with food every day in combination with standard-of-care pembrolizumab plus chemotherapy by IV infusion every 3 weeks.
Interventions
Oral Glutaminase Inhibitor
IV infusion
IV infusion
IV infusion
Orally, once daily beginning 7 days prior to the first dose of pemetrexed and continue until 21 days after the last dose of pemetrexed.
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.
For prophylaxis, orally twice per day (or equivalent). Taken the day before, day of, and day after pemetrexed administration.
Eligibility Criteria
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
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (102)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
University of South Alabama - Mitchell Cancer Center
Mobile, Alabama, 36604, United States
Yuma Regional Medical Center
Yuma, Arizona, 85364, United States
Compassionate Cancer Care
Fountain Valley, California, 92708, United States
St. Joseph Heritage Healthcare
Fullerton, California, 92835, United States
Loma Linda University Medical Center
Loma Linda, California, 92350, United States
University of Southern California (USC)
Los Angeles, California, 90033, United States
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
UCLA
Los Angeles, California, 90095, United States
University of California Irvine, Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
St. Joseph Heritage Healthcare - Santa Rosa
Santa Rosa, California, 95403, United States
Johns Hopkins Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016, United States
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016, United States
Boca Raton Regional Hospital Lynn Cancer Institute
Boca Raton, Florida, 33486, United States
Holy Cross Hospital - Bines Cancer Center
Fort Lauderdale, Florida, 33308, United States
Florida Cancer Specialist - South (SCRI)
Fort Myers, Florida, 33901, United States
Memorial Cancer Institute at Memorial Hospital West
Hollywood, Florida, 33021, United States
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, 33136, United States
Ocala Oncology Center
Ocala, Florida, 34474, United States
Florida Cancer Specialist - North (SCRI)
St. Petersburg, Florida, 33705, United States
Florida Cancer Specialist - Panhandle (SCRI)
Tallahassee, Florida, 32308, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Florida Cancer Specialist - East (SCRI)
West Palm Beach, Florida, 33401, United States
University Cancer and Blood Center
Athens, Georgia, 30607, United States
Piedmont Cancer Institute
Atlanta, Georgia, 30318, United States
Emory University Hospital
Atlanta, Georgia, 30322, United States
Northwest Georgia Oncology
Marietta, Georgia, 30060, United States
Hawaii Cancer Care
Honolulu, Hawaii, 96813, United States
Oncology of Northshore
Rolling Meadows, Illinois, 60008, United States
Orchard Healthcare Research Inc.
Skokie, Illinois, 60077, United States
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, 46804, United States
Beacon Health
South Bend, Indiana, 46601, United States
University of Kansas Medical Center (KUMC)
Westwood, Kansas, 66205, United States
Pontchartrain Cancer Center
Covington, Louisiana, 70443, United States
Johns Hopkins Bayview Memorial Hospital
Baltimore, Maryland, 21224, United States
Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817, United States
Maryland Oncology Hematology - USOR
Columbia, Maryland, 21044, United States
Frederick Health - James M. Stockman Cancer Institute
Frederick, Maryland, 21702, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Henry Ford Cancer Institute
Detroit, Michigan, 48202, United States
Bronson Methodist Hospital (West Michigan Cancer Center)
Kalamazoo, Michigan, 49001, United States
St. Joseph Mercy Hospital Cancer Care Center
Ypsilanti, Michigan, 48197, United States
Minnesota Oncology Hematology, P.A.
Coon Rapids, Minnesota, 55433, United States
Minnesota Oncology Hematology, P.A.
Edina, Minnesota, 55435, United States
Minnesota Oncology Hematology, P.A.
Maplewood, Minnesota, 55109, United States
Minnesota Oncology Hematology, P.A.
Minneapolis, Minnesota, 55404, United States
Minnesota Oncology Hematology, P.A.
Saint Paul, Minnesota, 55102, United States
Minnesota Oncology Hematology, P.A.
Woodbury, Minnesota, 55125, United States
Central Care Cancer Center
Bolivar, Missouri, 65613, United States
Washington University
St Louis, Missouri, 63110, United States
Nebraska Methodist Hospital
Omaha, Nebraska, 68114, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03766, United States
New Jersey Cancer Care and Blood Disorders (NJCCBD)
Belleville, New Jersey, 07109, United States
Summit Medical Group
Berkeley Heights, New Jersey, 07932, United States
The Valley Hospital - Luckow Pavilion
Paramus, New Jersey, 07652, United States
University of New Mexico Comprehensive Cancer Center
Albuquerque, New Mexico, 87131, United States
New York Oncology Hematology, P.C. (400 Patoon Creek Blvd.)
Albany, New York, 12206, United States
New York Oncology Hematology, P.C. (43 New Scotland Ave.)
Albany, New York, 12208, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263, United States
New York Oncology Hematology, P.C.
Clifton Park, New York, 12065, United States
Pelmutter Cancer Center at Winthrop
Mineola, New York, 11501, United States
New York University Langone (NYU)
New York, New York, 10016, United States
Columbia University Medical Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Weill Cornell Medical College - New York Presbyterian Hospital
New York, New York, 10065, United States
Cone Health at Alamance Regional
Burlington, North Carolina, 27215, United States
Cone Health Cancer Center
Greensboro, North Carolina, 27403, United States
Aultman Hospital
Canton, Ohio, 44710, United States
TriHealth Cancer Institute
Cincinnati, Ohio, 45220, United States
Ohio State University, James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210, United States
Ohio Health
Columbus, Ohio, 43214, United States
Toledo Clinic Cancer Center
Toledo, Ohio, 43623, United States
Oklahoma Cancer Specialists and Research Institute (OCSRI)
Tulsa, Oklahoma, 74146, United States
Providence Portland Medical Center
Portland, Oregon, 92713, United States
Oregon Health & Science University (OHSU) Knight Cancer Institute
Portland, Oregon, 97239, United States
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Pennsylvania State University Milton S. Hershey Medical Center
State College, Pennsylvania, 16801, United States
Sanford Health
Sioux Falls, South Dakota, 57104, United States
Tennessee Oncology - Chattanooga (SCRI)
Chattanooga, Tennessee, 37404, United States
Tennessee Oncology - Nashville (SCRI)
Nashville, Tennessee, 37203, United States
Texas Oncology - Austin Midtown
Austin, Texas, 78705, United States
Texas Oncology - Austin Central
Austin, Texas, 78731, United States
Texas Oncology - South Austin
Austin, Texas, 78745, United States
Texas Oncology Beaumont - USOR
Beaumont, Texas, 77701, United States
Texas Oncology - Denison
Denison, Texas, 75020, United States
Texas Oncology - Fort Worth Cancer Center
Fort Worth, Texas, 76104, United States
Oncology Consultants
Houston, Texas, 770390, United States
Oncology and Hematology of South Texas
Laredo, Texas, 78041, United States
Utah Cancer Specialist
Salt Lake City, Utah, 84106, United States
University of Utah - Huntsman Cancer Institute
Salt Lake City, Utah, 84112, United States
Oncology and Hematology Associates of Southwest Virginia
Blacksburg, Virginia, 24060, United States
Virginia Cancer Specialists
Fairfax, Virginia, 22031, United States
Oncology and Hematology Associates of Southwest Virginia
Low Moor, Virginia, 24457, United States
Virginia Commonwealth University (VCU) Massey Cancer Center
Richmond, Virginia, 23298, United States
Oncology and Hematology Associates of Southwest Virginia
Roanoke, Virginia, 24014, United States
Oncology and Hematology Associates of Southwest Virginia
Salem, Virginia, 24153, United States
Oncology and Hematology Associates of Southwest Virginia
Wytheville, Virginia, 24382, United States
University of Washington Seattle Cancer Care Alliance (SCCA)
Seattle, Washington, 98109, United States
Northwest Medical Specialities
Tacoma, Washington, 98405, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53705, United States
Froedtert Hospital and the Medical College of Wisconsin (MCW)
Milwaukee, Wisconsin, 53226, United States
Related Publications (1)
Aden D, Sureka N, Zaheer S, Chaurasia JK, Zaheer S. Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. Immunology. 2025 Jan;174(1):30-72. doi: 10.1111/imm.13871. Epub 2024 Oct 27.
PMID: 39462179DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Emil Kuriakose, MD
Calithera Biosciences, Inc
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Randomized, placebo controlled
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 7, 2020
First Posted
February 11, 2020
Study Start
July 24, 2020
Primary Completion
November 5, 2021
Study Completion
February 9, 2022
Last Updated
September 21, 2022
Record last verified: 2022-09
Data Sharing
- IPD Sharing
- Will not share