Clinical Trials /

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

NCT04265534

Description:

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.

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CX-839-014
  • NCT ID: NCT04265534

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

DrugSynonymsArms
TelaglenastatCB-839Telaglenastat with Pembrolizumab and Chemotherapy
Carboplatin ChemotherapyParaplatinPlacebo with Pembrolizumab and Chemotherapy
Pemetrexed ChemotherapyAlimtaPlacebo with Pembrolizumab and Chemotherapy
Pembrolizumab ImmunotherapyKeytrudaPlacebo with Pembrolizumab and Chemotherapy
PlaceboOral placeboPlacebo with Pembrolizumab and Chemotherapy
Dexamethasone 4 mgPlacebo with Pembrolizumab and Chemotherapy

Purpose

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 Arms

NameTypeDescriptionInterventions
Telaglenastat with Pembrolizumab and ChemotherapyExperimentalThe 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.
  • Telaglenastat
  • Carboplatin Chemotherapy
  • Pemetrexed Chemotherapy
  • Pembrolizumab Immunotherapy
  • Dexamethasone 4 mg
Placebo with Pembrolizumab and ChemotherapyPlacebo 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.
  • Carboplatin Chemotherapy
  • Pemetrexed Chemotherapy
  • Pembrolizumab Immunotherapy
  • Placebo
  • Dexamethasone 4 mg

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS), Assessed by Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame:Up to 24 months
Safety Issue:
Description:Duration of investigator-determined PFS per RECIST v1.1 in the intent-to-treat (ITT) population

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:DOR is defined as the duration of response for patients achieving a CR or PR
Measure:Overall Survival
Time Frame:Up to 55 months
Safety Issue:
Description:
Measure:PFS in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:ORR in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:DOR in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:OS in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway
Time Frame:Up to 55 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Calithera Biosciences, Inc

Trial Keywords

  • NSCLC
  • KEAP1
  • NRF2
  • NFE2l2
  • LKB1
  • STK11
  • Next Generation Sequencing
  • NGS
  • Mutation
  • Pembrolizumab
  • Pemetrexed
  • Carboplatin
  • Randomized
  • Placebo
  • Chemotherapy
  • Targeted Therapy
  • Telaglenastat
  • Glutamine
  • Glutaminase
  • Glutathione
  • Immunotherapy
  • Front-line
  • First-line
  • Non-squamous
  • Keytruda
  • Alimta
  • Guardant360

Last Updated

July 17, 2020