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

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

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.

Study Overview

• Status: Terminated
• Conditions: Melanoma; Non-small Cell Lung Cancer (NSCLC); Clear Cell Renal Cell Carcinoma (ccRCC)
• Intervention / Treatment: Drug: CB-839; Drug: Nivolumab

Detailed Description

This study is an open-label Phase 1/ 2 evaluation of CB-839 in combination with nivolumab in patients with clear cell renal cell carcinoma, melanoma, and non-small cell lung cancer.

During Phase 1, patients will be enrolled into escalating dose cohorts to determine the recommended phase 2 dose (RP2D).

In Phase 2, patients with clear cell renal cell carcinoma, melanoma, and non-small cell lung cancer will be enrolled into separate cohorts.

All patients will be assessed for safety, pharmacokinetics, biomarkers and tumor response.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85016
      • Honor Health
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer Blood Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02114
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Caner Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10016
      • New York University
    • New York, New York, United States, 10655
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance/University of Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	Drug: CB-839; Glutaminase inhibitor; Other Names: telaglenastat; Drug: Nivolumab; PD-1 inhibitor; Other Names: BMS-936558; Opdivo
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.	Drug: CB-839; Glutaminase inhibitor; Other Names: telaglenastat; Drug: Nivolumab; PD-1 inhibitor; Other Names: BMS-936558; Opdivo
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.	Drug: CB-839; Glutaminase inhibitor; Other Names: telaglenastat; Drug: Nivolumab; PD-1 inhibitor; Other Names: BMS-936558; Opdivo
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.	Drug: CB-839; Glutaminase inhibitor; Other Names: telaglenastat; Drug: Nivolumab; PD-1 inhibitor; Other Names: BMS-936558; Opdivo
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.	Drug: CB-839; Glutaminase inhibitor; Other Names: telaglenastat; Drug: Nivolumab; PD-1 inhibitor; Other Names: BMS-936558; Opdivo
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.	Drug: CB-839; Glutaminase inhibitor; Other Names: telaglenastat; Drug: Nivolumab; PD-1 inhibitor; Other Names: BMS-936558; Opdivo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	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.
Number of Participants With Clinically Significant Treatment-Emergent Values in Hematology, Serum Chemistry Panel, Vital Signs or Weight	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.	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.
Overall Response Rate (ORR) Per Investigator Assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	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.	up to a maximum of 2.8 years
Duration of Response (DOR) Per Investigator Assessed RECIST v1.1	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.	up to a maximum of 2.8 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) Per RECIST v1.1	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.	up to a maximum of 2.8 years
Overall Survival	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.	up to a maximum of 2.8 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Actual): April 24, 2020
• Study Completion (Actual): April 24, 2020

Study Registration Dates

• First Submitted: May 6, 2016
• First Submitted That Met QC Criteria: May 12, 2016
• First Posted (Estimate): May 13, 2016

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: February 21, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; RCC; Tumor Metabolism; Glutaminase Inhibitor; Melanoma (MEL); Immuno-Oncology; Glutaminase
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Kidney Neoplasms; Neuroendocrine Tumors; Nevi and Melanomas; Carcinoma, Renal Cell; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CX-839-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO