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

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ClinicalTrials.gov Identifier: NCT04265534
Recruitment Status : Recruiting
First Posted : February 11, 2020
Last Update Posted : June 1, 2021
Sponsor:
Information provided by (Responsible Party):
Calithera Biosciences, Inc

Tracking Information
First Submitted Date  ICMJE February 7, 2020
First Posted Date  ICMJE February 11, 2020
Last Update Posted Date June 1, 2021
Actual Study Start Date  ICMJE July 24, 2020
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2020)
  • Progression-Free Survival (PFS), Assessed by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to 24 months ]
    Duration of investigator-determined PFS per RECIST v1.1 in the intent-to-treat (ITT) population
  • 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 [ Time Frame: 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 [ Time Frame: Up to 6 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2020)
  • 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 [ Time Frame: Up to 24 months ]
    ORR is defined as the percentage of patients with complete response (CR) or partial response (PR) according to the RECIST v1.1 criteria as assessed by the investigator.
  • 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 [ Time Frame: Up to 24 months ]
    DOR is defined as the duration of response for patients achieving a CR or PR
  • Overall Survival [ Time Frame: Up to 55 months ]
  • PFS in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway [ Time Frame: Up to 24 months ]
  • ORR in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway [ Time Frame: Up to 24 months ]
  • DOR in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway [ Time Frame: Up to 24 months ]
  • OS in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway [ Time Frame: Up to 55 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE KEAPSAKE: A Study of Telaglenastat (CB-839) With Standard-of-Care Chemoimmunotherapy in 1L KEAP1/NRF2-Mutated, Nonsquamous NSCLC
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Randomized, placebo controlled
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Telaglenastat
    Oral Glutaminase Inhibitor
    Other Name: CB-839
  • Drug: Carboplatin Chemotherapy
    IV infusion
    Other Name: Paraplatin
  • Drug: Pemetrexed Chemotherapy
    IV infusion
    Other Name: Alimta
  • Biological: Pembrolizumab Immunotherapy
    IV infusion
    Other Name: Keytruda
  • Drug: Placebo
    Oral placebo
    Other Name: 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.
Study Arms  ICMJE
  • Experimental: Telaglenastat with Pembrolizumab and Chemotherapy
    The 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.
    Interventions:
    • Drug: Telaglenastat
    • Drug: Carboplatin Chemotherapy
    • Drug: Pemetrexed Chemotherapy
    • Biological: Pembrolizumab Immunotherapy
    • Dietary Supplement: Folic acid 400 -1000 μg
    • Dietary Supplement: Vitamin B12 1000 μg
    • Drug: Dexamethasone 4 mg
  • Placebo Comparator: Placebo with Pembrolizumab and Chemotherapy
    Placebo 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:
    • Drug: Carboplatin Chemotherapy
    • Drug: Pemetrexed Chemotherapy
    • Biological: Pembrolizumab Immunotherapy
    • Drug: Placebo
    • Dietary Supplement: Folic acid 400 -1000 μg
    • Dietary Supplement: Vitamin B12 1000 μg
    • Drug: Dexamethasone 4 mg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 10, 2020)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2024
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically documented nonsquamous NSCLC
  • Stage IV (M1a-c, AJCC 8th Edition) disease not previously treated with systemic therapy for metastatic NSCLC

    a. 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

Exclusion Criteria:

  • Squamous cell histology and mixed histology tumors with any small-cell component (other mixed histology and large cell neuroendocrine histology is allowed).
  • Known history of malignancy within the past three years except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or other neoplasm that, in the opinion of the principal investigator and with the agreement of the medical monitor, will not interfere with study-specific endpoints.
  • Had radiation therapy to the lung > 30 Gy within 6 months prior to randomization.
  • Has active autoimmune disease that has required systemic treatment in past 2 years.
  • Is currently receiving chronic systemic steroids and/or immunosuppressive drugs.
  • Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
  • Unable to swallow oral medications.
  • Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb).
  • Known positivity for Hepatitis B or C.
  • Is unable or unwilling to take folic acid or vitamin B12 supplementation.
  • Interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoid treatment.
  • Unable or unwilling to discontinue proton pump inhibitors (PPI) at least 5 days before randomization.
  • Major surgery within 3 weeks of randomization.
  • Symptomatic ascites or pleural effusion.
  • Any condition that may preclude adequate absorption of oral study drug.
  • Patients with active and/or untreated central nervous system metastasis including carcinomatous meningitis (leptomeningeal disease) are not eligible. Patients with previously treated brain metastases are eligible if they meet the following criteria:

    1. Received definitive treatment with stereotactic radiosurgery (SRS) or surgery to all known central nervous system (CNS) lesions (whole brain radiotherapy is not an eligible modality)
    2. Are at least 7 days post SRS and 4 weeks post-surgical resection of CNS disease, symptomatically stable and off steroids before randomization
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Clinical Administrator 650-870-1000 info@keapsakeclinicaltrial.com
Contact: Clinical Admin info@keapsakeclinicaltrial.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04265534
Other Study ID Numbers  ICMJE CX-839-014
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Calithera Biosciences, Inc
Study Sponsor  ICMJE Calithera Biosciences, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Emil Kuriakose, MD Calithera Biosciences, Inc
PRS Account Calithera Biosciences, Inc
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP