Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    (NCT04265534)
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04265534
Recruitment Status : Not yet recruiting
First Posted : February 11, 2020
Last Update Posted : February 11, 2020
Sponsor:
Information provided by (Responsible Party):
Calithera Biosciences, Inc

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.

Condition or disease Intervention/treatment Phase
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 Drug: Telaglenastat 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 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Randomized, placebo controlled
Primary Purpose: Treatment
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)
Estimated Study Start Date : April 2020
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
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

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.

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.
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.




Primary Outcome Measures :
  1. 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

  2. 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 ]
  3. 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 ]

Secondary Outcome Measures :
  1. 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.

  2. 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

  3. Overall Survival [ Time Frame: Up to 55 months ]
  4. PFS in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway [ Time Frame: Up to 24 months ]
  5. ORR in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway [ Time Frame: Up to 24 months ]
  6. DOR in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway [ Time Frame: Up to 24 months ]
  7. OS in the Subgroup of Patients with Biochemical Evidence of Activation of the NRF2 Pathway [ Time Frame: Up to 55 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 inhibitor (PPI) use 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04265534


Contacts
Layout table for location contacts
Contact: Clinical Administrator 650-870-1000 clinicaltrials@calithera.com
Contact: Clinical Admin clinicaltrials@calithera.com

Sponsors and Collaborators
Calithera Biosciences, Inc
Investigators
Layout table for investigator information
Study Director: Sam Whiting, MD, PhD Calithera Biosciences, Inc
Layout table for additonal information
Responsible Party: Calithera Biosciences, Inc
ClinicalTrials.gov Identifier: NCT04265534    
Other Study ID Numbers: CX-839-014
First Posted: February 11, 2020    Key Record Dates
Last Update Posted: February 11, 2020
Last Verified: February 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Calithera Biosciences, Inc:
NSCLC
KEAP1
NERF2
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Folic Acid
Vitamin B 12
Hydroxocobalamin
Dexamethasone
Carboplatin
Pembrolizumab
Pemetrexed
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists