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

NCT02771626 | Terminated Phase 1 Results

• 1 other identifier: CX-839-004
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 17

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.

Conditions

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

Keywords

RCC; Melanoma (MEL); NSCLC; Immuno-Oncology; Tumor Metabolism; Glutaminase; Glutaminase Inhibitor

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• Progression-Free Survival (PFS) Per RECIST v1.1

  up to a maximum of 2.8 years

• Overall Survival

  up to a maximum of 2.8 years

Study Arms (6)

Telaglenastat 600 mg + Standard Dose Nivolumab

EXPERIMENTAL

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; Drug: Nivolumab

Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Naïve to Checkpoint Inhibitors

EXPERIMENTAL

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; Drug: Nivolumab

Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Recently Treated With Nivolumab

EXPERIMENTAL

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; Drug: Nivolumab

Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC With Prior PD-1 Therapy

EXPERIMENTAL

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; Drug: Nivolumab

Telaglenastat 800 mg + Standard Dose Nivolumab: Melanoma With Prior PD-1 Therapy

EXPERIMENTAL

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; Drug: Nivolumab

Telaglenastat 800 mg + Standard Dose Nivolumab: NSCLC With Prior PD-1 Therapy

EXPERIMENTAL

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; Drug: Nivolumab

Interventions

CB-839 DRUG

Glutaminase inhibitor

Also known as: telaglenastat

Telaglenastat 600 mg + Standard Dose Nivolumab; Telaglenastat 800 mg + Standard Dose Nivolumab: Melanoma With Prior PD-1 Therapy; Telaglenastat 800 mg + Standard Dose Nivolumab: NSCLC With Prior PD-1 Therapy; Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Naïve to Checkpoint Inhibitors; Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Recently Treated With Nivolumab; Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC With Prior PD-1 Therapy

Nivolumab DRUG

PD-1 inhibitor

Also known as: Opdivo, BMS-936558

Telaglenastat 600 mg + Standard Dose Nivolumab; Telaglenastat 800 mg + Standard Dose Nivolumab: Melanoma With Prior PD-1 Therapy; Telaglenastat 800 mg + Standard Dose Nivolumab: NSCLC With Prior PD-1 Therapy; Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Naïve to Checkpoint Inhibitors; Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Recently Treated With Nivolumab; Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC With Prior PD-1 Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (17)

Honor Health

Scottsdale, Arizona, 85016, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University Cancer Blood Center

Athens, Georgia, 30607, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02114, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Caner Center

Detroit, Michigan, 48201, United States

Location

New York University

New York, New York, 10016, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10655, United States

Location

University Hospitals Cleveland

Cleveland, Ohio, 44106, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance/University of Washington

Seattle, Washington, 98109, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Related Publications (1)

• Aden D, Sureka N, Zaheer S, Chaurasia JK, Zaheer S. Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. Immunology. 2025 Jan;174(1):30-72. doi: 10.1111/imm.13871. Epub 2024 Oct 27.

  PMID: 39462179 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Melanoma; Carcinoma, Non-Small-Cell Lung

Interventions

CB-839; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Calithera Biosciences, Inc

clinicaltrials@calithera.com

650-870-1000

Study Officials

• Sam Whiting, MD, PhD

  Calithera Biosciences, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2016
• First Posted: May 13, 2016
• Study Start: August 1, 2016
• Primary Completion: April 24, 2020
• Study Completion: April 24, 2020
• Last Updated: March 17, 2023
• Results First Posted: March 17, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)