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

Study Overview
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Brief Summary
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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.

Official Title
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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

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

Intervention / Treatment
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* Drug: CB-839
* Drug: Nivolumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telaglenastat 600 mg + Standard Dose Nivolumab<br>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<br>* Glutaminase inhibitor<br>* Other names: telaglenastat;Drug: Nivolumab<br>* PD-1 inhibitor<br>* Other names: BMS-936558;|
| Experimental: Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Naïve to Checkpoint Inhibitors<br>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<br>* Glutaminase inhibitor<br>* Other names: telaglenastat;Drug: Nivolumab<br>* PD-1 inhibitor<br>* Other names: BMS-936558;|
| Experimental: Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Recently Treated With Nivolumab<br>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<br>* Glutaminase inhibitor<br>* Other names: telaglenastat;Drug: Nivolumab<br>* PD-1 inhibitor<br>* Other names: BMS-936558;|
| Experimental: Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC With Prior PD-1 Therapy<br>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<br>* Glutaminase inhibitor<br>* Other names: telaglenastat;Drug: Nivolumab<br>* PD-1 inhibitor<br>* Other names: BMS-936558;|
| Experimental: Telaglenastat 800 mg + Standard Dose Nivolumab: Melanoma With Prior PD-1 Therapy<br>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<br>* Glutaminase inhibitor<br>* Other names: telaglenastat;Drug: Nivolumab<br>* PD-1 inhibitor<br>* Other names: BMS-936558;|
| Experimental: Telaglenastat 800 mg + Standard Dose Nivolumab: NSCLC With Prior PD-1 Therapy<br>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<br>* Glutaminase inhibitor<br>* Other names: telaglenastat;Drug: Nivolumab<br>* PD-1 inhibitor<br>* Other names: BMS-936558;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RCC, Melanoma (MEL), NSCLC, Immuno-Oncology, Tumor Metabolism, Glutaminase, Glutaminase Inhibitor