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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 118
- 试验地点
- 17
- 主要终点
- 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)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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).
干预措施: CB-839 (Drug)
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).
干预措施: Nivolumab (Drug)
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.
干预措施: CB-839 (Drug)
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.
干预措施: Nivolumab (Drug)
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.
干预措施: CB-839 (Drug)
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.
干预措施: Nivolumab (Drug)
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.
干预措施: CB-839 (Drug)
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.
干预措施: Nivolumab (Drug)
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.
干预措施: CB-839 (Drug)
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.
干预措施: Nivolumab (Drug)
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.
干预措施: CB-839 (Drug)
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.
干预措施: Nivolumab (Drug)
结局指标
主要结局
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)
时间窗: 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.
Overall Response Rate (ORR) Per Investigator Assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
时间窗: 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.
Number of Participants With Clinically Significant Treatment-Emergent Values in Hematology, Serum Chemistry Panel, Vital Signs or Weight
时间窗: 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.
Duration of Response (DOR) Per Investigator Assessed RECIST v1.1
时间窗: 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.
次要结局
- 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)