Back to resultsStudy CB-839 in Combination With Nivolumab in Patients With Melanoma, Clear Cell Renal Cell Carcinoma (ccRCC) and Non-Small Cell Lung Cancer (NSCLC)
Primary Purpose
Clear Cell Renal Cell Carcinoma (ccRCC), Melanoma, Non-small Cell Lung Cancer (NSCLC)
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CB-839
Nivolumab
Sponsored by
About this trial
This is an interventional treatment trial for Clear Cell Renal Cell Carcinoma (ccRCC) focused on measuring RCC, Melanoma (MEL), NSCLC, Immuno-Oncology, Tumor Metabolism, Glutaminase, Glutaminase Inhibitor
Eligibility Criteria
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
Sites / Locations
- Honor Health
- Stanford University
- University of Colorado
- University Cancer Blood Center
- Beth Israel Deaconess Medical Center
- Massachusetts General Hospital
- Dana-Farber Cancer Institute
- Karmanos Caner Center
- New York University
- Columbia University Medical Center
- Memorial Sloan Kettering Cancer Center
- University Hospitals Cleveland
- University of Pennsylvania
- Vanderbilt University
- University of Texas MD Anderson Cancer Center
- Seattle Cancer Care Alliance/University of Washington
- Northwest Medical Specialties
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Telaglenastat 600 mg + Standard Dose Nivolumab
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
Telaglenastat 800 mg + Standard Dose Nivolumab: Melanoma With Prior PD-1 Therapy
Telaglenastat 800 mg + Standard Dose Nivolumab: NSCLC With Prior PD-1 Therapy
Arm Description
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).
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT02771626
First Posted
May 6, 2016
Last Updated
February 21, 2023
Sponsor
Calithera Biosciences, Inc
1. Study Identification
Unique Protocol Identification Number
NCT02771626
Brief Title
Study CB-839 in Combination With Nivolumab in Patients With Melanoma, Clear Cell Renal Cell Carcinoma (ccRCC) and Non-Small Cell Lung Cancer (NSCLC)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Terminated
Why Stopped
lack of efficacy
Study Start Date
August 1, 2016 (Actual)
Primary Completion Date
April 24, 2020 (Actual)
Study Completion Date
April 24, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Calithera Biosciences, Inc
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
118 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Telaglenastat 600 mg + Standard Dose Nivolumab
Arm Type
Experimental
Arm Description
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).
Arm Title
Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Naïve to Checkpoint Inhibitors
Arm Type
Experimental
Arm Description
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.
Arm Title
Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Recently Treated With Nivolumab
Arm Type
Experimental
Arm Description
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.
Arm Title
Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC With Prior PD-1 Therapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Telaglenastat 800 mg + Standard Dose Nivolumab: Melanoma With Prior PD-1 Therapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Telaglenastat 800 mg + Standard Dose Nivolumab: NSCLC With Prior PD-1 Therapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
CB-839
Other Intervention Name(s)
telaglenastat
Intervention Description
Glutaminase inhibitor
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo, BMS-936558
Intervention Description
PD-1 inhibitor
Primary Outcome Measure Information:
Title
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)
Description
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.
Title
Number of Participants With Clinically Significant Treatment-Emergent Values in Hematology, Serum Chemistry Panel, Vital Signs or Weight
Description
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.
Title
Overall Response Rate (ORR) Per Investigator Assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Description
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.
Time Frame
up to a maximum of 2.8 years
Title
Duration of Response (DOR) Per Investigator Assessed RECIST v1.1
Description
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.
Time Frame
up to a maximum of 2.8 years
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS) Per RECIST v1.1
Description
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
Title
Overall Survival
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sam Whiting, MD, PhD
Organizational Affiliation
Calithera Biosciences, Inc
Official's Role
Study Director
Facility Information:
Facility Name
Honor Health
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University Cancer Blood Center
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Karmanos Caner Center
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
New York University
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10655
Country
United States
Facility Name
University Hospitals Cleveland
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Cancer Care Alliance/University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Northwest Medical Specialties
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study CB-839 in Combination With Nivolumab in Patients With Melanoma, Clear Cell Renal Cell Carcinoma (ccRCC) and Non-Small Cell Lung Cancer (NSCLC)
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