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

Phase 2TerminatedNCT02771626

Calithera Biosciences, Inc118 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

118

Conditions

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

Interventions

CB-839DRUG

Glutaminase inhibitor

NivolumabDRUG

PD-1 inhibitor

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (17)

Honor Health

Scottsdale, Arizona, United States

Stanford University

Palo Alto, California, United States

Outcomes

Primary Outcomes

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.

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.

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.

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.

Overall Response Rate (ORR) Per Investigator Assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 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.

Time frame: up to a maximum of 2.8 years