Study CB-839 in Combination With Nivolumab in Patients With Melanoma, Clear Cell Renal Cell Carcinoma (ccRCC) and Non-Small Cell Lung Cancer (NSCLC)

• ClinicalTrials.gov Identifier: NCT02771626
• Recruitment Status: Terminated
• First Posted: May 13, 2016
• Results First Posted: March 17, 2023
• Last Update Posted: March 17, 2023
• Sponsor: Calithera Biosciences, Inc
• Information provided by (Responsible Party): Calithera Biosciences, Inc

Tracking Information

• First Submitted Date: May 6, 2016
• First Posted Date: May 13, 2016
• Results First Submitted Date: January 23, 2023
• Results First Posted Date: March 17, 2023
• Last Update Posted Date: March 17, 2023
• Actual Study Start Date: August 1, 2016
• Actual Primary Completion Date: April 24, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 21, 2023)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Dose Interruption, Reduction, or Study Drug Discontinuation (Excluding Grade 5 Disease Progression) [ Time Frame: From the first dose of study drug up to 28 days post last dose. Median duration of telaglenastat treatment was 92 days and that for nivolumab treatment was 84 days. ]
  An adverse event (AE) is any untoward, undesired, or unplanned event that does not need to be causally related to treatment. A serious adverse event (SAE) is an AE that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in a persistent or significant disability or incapacity, results in a congenital anomaly or birth defect, or important medical events that may not result in death, be life-threatening, or require hospitalization may be considered SAEs when, based on appropriate medical judgment, they may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. Relatedness to study medication was graded as either, probably, possibly, unlikely, or unrelated. Events were categorized according to the Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death.
• Number of Participants With Clinically Significant Treatment-Emergent Values in Hematology, Serum Chemistry Panel, Vital Signs or Weight [ Time Frame: From the first dose of study drug up to 28 days post last dose. Median duration of telaglenastat treatment was 92 days and that for nivolumab treatment was 84 days. ]
  Hematology assessments included: hemoglobin; hematocrit, red blood cell count, white blood cell count with differential, and platelet count. Serum chemistry panel included: sodium, potassium, chloride, carbon dioxide, calcium, glucose, blood urea nitrogen, total protein, albumin, total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatinine, thyroid stimulating hormone. Vital sign assessments included systolic and diastolic blood pressures, pulse (heart) rate, respiratory rate, temperature, and body weight.
• Overall Response Rate (ORR) Per Investigator Assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: up to a maximum of 2.8 years ]
  ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR or PR was required to be sustained for 4 weeks when confirmation was reported.

  • CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.
  • PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
• Duration of Response (DOR) Per Investigator Assessed RECIST v1.1 [ Time Frame: up to a maximum of 2.8 years ]
  DOR is defined as the time between the first documentation of a PR or a CR to the first documentation of progressive disease (PD) or death, whichever occurred first. DOR was censored at the date of last radiographic disease if the patient was alive and progression free at the time of database lock, PD, or death occurred after missing data for 2 consecutive radiographic disease assessments, or patient received non-protocol treatment prior to documentation of disease progression.

  • CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.
  • PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
  • PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Original Primary Outcome Measures (submitted: May 12, 2016)

• Safety and Tolerability of CB-839 and Nivolumab: Incidence of adverse events [ Time Frame: Every 28 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months ]
• Efficacy of CB-839 in Combination with Nivolumab: change in tumor size from baseline [ Time Frame: Every 28 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months ]

Current Secondary Outcome Measures (submitted: February 21, 2023)

• Progression-Free Survival (PFS) Per RECIST v1.1 [ Time Frame: up to a maximum of 2.8 years ]
  PFS was defined as time from the first dose date to the earlier of either PD per RECIST v1.1 or death from any cause. The duration of PFS was censored at the date of last radiographic disease if the patient was alive and progression-free at the time of analysis data cutoff, disease progression, or death occurred after missing data for 2 consecutive radiographic disease assessments, or patient received non-protocol treatment prior to documentation of disease progression. - PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
• Overall Survival [ Time Frame: up to a maximum of 2.8 years ]
  Overall survival was defined as the time from the first dose date to death due to any cause. For participants alive at time of analysis, overall survival was censored at the time when the participant was last known to be alive.

Original Secondary Outcome Measures (submitted: May 12, 2016)

• Recommended Phase 2 Dose (RP2D) of CB-839 in Combination with Nivolumab [ Time Frame: 12 Weeks ]
  A minimum of 9-12 patients with ccRCC, melanoma, or NSCLC will be enrolled in Dose Escalation to determine RP2D.
• Maximum plasma concentration of CB-839 in combination with Nivolumab [ Time Frame: Every 28 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months ]
  Non-compartmental method of analysis will be used to analyze the plasma concentrations of CB-839.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study CB-839 in Combination With Nivolumab in Patients With Melanoma, Clear Cell Renal Cell Carcinoma (ccRCC) and Non-Small Cell Lung Cancer (NSCLC)
• Official Title: A Phase 1/2 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the Glutaminase Inhibitor CB-839 in Combination With Nivolumab in Patients With Advanced/Metastatic Melanoma, Renal Cell Carcinoma and Non-Small Cell Lung Cancer
• Brief Summary: This study is an open-label Phase 1/2 evaluation of CB-839 in combination with nivolumab in participants with clear cell renal cell carcinoma, melanoma, and non-small cell lung cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Factorial Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Clear Cell Renal Cell Carcinoma (ccRCC)
• Melanoma
• Non-small Cell Lung Cancer (NSCLC)

Intervention

• Drug: CB-839
  Glutaminase inhibitor
  Other Name: telaglenastat
• Drug: Nivolumab
  PD-1 inhibitor
  Other Names:

  • Opdivo
  • BMS-936558

Study Arms

• Experimental: Telaglenastat 600 mg + Standard Dose Nivolumab
  Telaglenastat 600 mg in combination with standard dose nivolumab in participants with advanced/metastatic clear cell renal cell carcinoma (ccRCC), melanoma, and non-small cell lung cancer (NSCLC).
  Interventions:

  • Drug: CB-839
  • Drug: Nivolumab
• Experimental: Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Naïve to Checkpoint Inhibitors
  Telaglenastat 800 mg/standard dose nivolumab combination in participants with advanced/metastatic ccRCC who have previously received at least one tyrosine kinase inhibitor (TKI) but are treatment naïve to checkpoint modulators programmed death-1/programmed death ligand-1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or any other agent that specifically targets a T-cell checkpoint or co-stimulation pathway.
  Interventions:

  • Drug: CB-839
  • Drug: Nivolumab
• Experimental: Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Recently Treated With Nivolumab
  Telaglenastat 800 mg/standard dose nivolumab combination in participants with advanced/metastatic ccRCC who received nivolumab in most recent treatment line that had documented radiological disease progression OR are currently receiving nivolumab with stable disease for at least 24 weeks.
  Interventions:

  • Drug: CB-839
  • Drug: Nivolumab
• Experimental: Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC With Prior PD-1 Therapy
  Telaglenastat 800 mg/standard dose nivolumab combination in participants with advanced/metastatic ccRCC that had documented radiological disease progression while receiving an anti-PD-1/PD-L1 therapy in any prior line of therapy.
  Interventions:

  • Drug: CB-839
  • Drug: Nivolumab
• Experimental: Telaglenastat 800 mg + Standard Dose Nivolumab: Melanoma With Prior PD-1 Therapy
  Telaglenastat 800 mg/standard dose nivolumab combination in participants with unresectable or metastatic melanoma that had documented radiological disease progression while receiving an anti-PD-1 therapy in their most recent line of therapy.
  Interventions:

  • Drug: CB-839
  • Drug: Nivolumab
• Experimental: Telaglenastat 800 mg + Standard Dose Nivolumab: NSCLC With Prior PD-1 Therapy
  Telaglenastat 800 mg/standard dose nivolumab combination in participants with NSCLC that does not harbor an activating mutation in the epidermal growth factor receptor (EGFR) oncogene and who received nivolumab in most recent treatment line and had documented radiological disease progression OR are currently receiving nivolumab with Stable Disease for at least 24 weeks.
  Interventions:

  • Drug: CB-839
  • Drug: Nivolumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 28, 2020): 118
• Original Estimated Enrollment (submitted: May 12, 2016): 242
• Actual Study Completion Date: April 24, 2020
• Actual Primary Completion Date: April 24, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Addition eligibility criteria based on tumor type apply

Inclusion Criteria:

• Ability to provide written informed consent in accordance with federal, local, and institutional guidelines
• Histological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Life Expectancy of at least 3 months
• Adequate hepatic, renal, cardiac, and hematologic function
• Measurable disease by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria
• Resolution of treatment-related toxicities except alopecia

Exclusion Criteria:

• Unable to receive oral medications
• Unable to receive oral or intravenous (IV) hydration
• Intolerance to prior anti-PD-1/PD-L1 therapy
• Prior severe hypersensitivity reaction to another monoclonal antibody (mAb)
• Any other current or previous malignancy within 3 years except protocol allowed malignancies
• Chemotherapy, TKI therapy, radiation therapy or hormonal therapy within 2 weeks
• Immunotherapy or biological therapy, or investigational agent within 3 weeks (Note: Some cohort exceptions allow anti-PD-1 therapy)
• Active known or suspected exclusionary autoimmune disease
• Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other systemic immunosuppressive medications within 2 weeks
• History of known risks factors for bowel perforation
• Symptomatic ascites or pleural effusion
• Major surgery within 28 days before Cycle 1 Day 1
• Active infection requiring parenteral antibiotics, antivirals, or antifungals within 2 weeks prior to first dose of study drug
• Patients who have human immunodeficiency virus (HIV), Hepatitis B or C
• Conditions that could interfere with treatment or protocol-related procedures
• Active and/or untreated central nervous system (CNS) disease or non-stable brain metastases

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02771626
• Other Study ID Numbers: CX-839-004
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Calithera Biosciences, Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Calithera Biosciences, Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Sam Whiting, MD, PhD; Calithera Biosciences, Inc

• PRS Account: Calithera Biosciences, Inc
• Verification Date: February 2023