Study CB-839 in Combination With Nivolumab in Patients Wi... | NCT02771626

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
CB-839	Drug	Glutaminase inhibitor	Telaglenastat 600 mg + Standard Dose Nivolumab Telaglenastat 800 mg + Standard Dose Nivolumab: Melanoma With Prior PD-1 Therapy

Outcomes Module

Primary Outcomes

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

Secondary Outcomes

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.

Eligibility Module

Name	Affiliation	Role
Sam Whiting, MD, PhD	Calithera Biosciences, Inc	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Honor Health		Scottsdale	Arizona	85016	United States
Stanford University

PubMed Identifier	Type	Citation	Retractions
39462179	Derived	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.

ID	Title	Description
FG000	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).
FG001	Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Naïve to Checkpoint Inhibitors

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 14, 2017	Jan 23, 2023

Arm/Group Information

ID	Title	Description
BG000	Telaglenastat 600 mg + Standard Dose Nivolumab	Telaglenastat 600 mg in combination with standard dose nivolumab in participants with advanced/metastatic ccRCC, melanoma, and NSCLC.
BG001	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 TKI but are treatment naïve to checkpoint modulators PD-1/PD-L1, CTLA-4, or any other agent that specifically targets a T-cell checkpoint or co-stimulation pathway.
BG002	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.
BG003	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.
BG004	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.
BG005	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 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.
BG006	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Posted

Count of Participants

Participants

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.

ID	Title	Description
OG000	Telaglenastat 600 mg + Standard Dose Nivolumab	Telaglenastat 600 mg in combination with standard dose nivolumab in participants with advanced/metastatic ccRCC, melanoma, and NSCLC.
OG001	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 TKI but are treatment naïve to checkpoint modulators PD-1/PD-L1, CTLA-4, or any other agent that specifically targets a T-cell checkpoint or co-stimulation pathway.
OG002	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.
OG003	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.
OG004	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.

Units	Counts
Participants	OG0008 OG00126 OG00217 OG003

Title

Denominators

Categories

≥ 1 TEAE

Title	Measurements
	OG0008 OG00126 OG00217 OG003

Primary

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.

Posted

Count of Participants

Participants

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.

ID	Title	Description
OG000	Telaglenastat 600 mg + Standard Dose Nivolumab	Telaglenastat 600 mg in combination with standard dose nivolumab in participants with advanced/metastatic ccRCC, melanoma, and NSCLC.
OG001	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 TKI but are treatment naïve to checkpoint modulators PD-1/PD-L1, CTLA-4, or any other agent that specifically targets a T-cell checkpoint or co-stimulation pathway.

Primary

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.

Posted

Number

95% Confidence Interval

percentage of participants

up to a maximum of 2.8 years

ID	Title	Description
OG000	Telaglenastat 600 mg + Standard Dose Nivolumab	Telaglenastat 600 mg in combination with standard dose nivolumab in participants with advanced/metastatic ccRCC, melanoma, and NSCLC.
OG001	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 TKI but are treatment naïve to checkpoint modulators PD-1/PD-L1, CTLA-4, or any other agent that specifically targets a T-cell checkpoint or co-stimulation pathway.
OG002	Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Recently Treated With Nivolumab

Primary

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.

Participants with a response.

Posted

Median

95% Confidence Interval

months

up to a maximum of 2.8 years

ID	Title	Description
OG000	Telaglenastat 600 mg + Standard Dose Nivolumab	Telaglenastat 600 mg in combination with standard dose nivolumab in participants with advanced/metastatic ccRCC, melanoma, and NSCLC.
OG001	Telaglenastat 800 mg + Standard Dose Nivolumab: ccRCC Naïve to Checkpoint Inhibitors

Secondary

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.

Participants with an event (PD per RECIST v1.1 or death from any cause).

Posted

Median

95% Confidence Interval

months

up to a maximum of 2.8 years

ID	Title	Description
OG000	Telaglenastat 600 mg + Standard Dose Nivolumab	Telaglenastat 600 mg in combination with standard dose nivolumab in participants with advanced/metastatic ccRCC, melanoma, and NSCLC.
OG001	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 TKI but are treatment naïve to checkpoint modulators PD-1/PD-L1, CTLA-4, or any other agent that specifically targets a T-cell checkpoint or co-stimulation pathway.

Secondary

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.

Posted

Median

95% Confidence Interval

months

up to a maximum of 2.8 years

ID	Title	Description
OG000	Telaglenastat 600 mg + Standard Dose Nivolumab	Telaglenastat 600 mg in combination with standard dose nivolumab in participants with advanced/metastatic ccRCC, melanoma, and NSCLC.
OG001	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 TKI but are treatment naïve to checkpoint modulators PD-1/PD-L1, CTLA-4, or any other agent that specifically targets a T-cell checkpoint or co-stimulation pathway.
OG002	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Telaglenastat 600 mg + Standard Dose Nivolumab	Telaglenastat 600 mg in combination with standard dose nivolumab in participants with advanced/metastatic ccRCC, melanoma, and NSCLC.	3	8	2	8	8	8
EG001	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 TKI but are treatment naïve to checkpoint modulators PD-1/PD-L1, CTLA-4, or any other agent that specifically targets a T-cell checkpoint or co-stimulation pathway.	15	26	8	26	26	26
EG002	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.	11	17	6	17	15	17
EG003	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.	3	9	1	9	9	9
EG004	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.	27	37	12	37	36	37
EG005	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 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.	16	21	7	21	21	21

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0012 affected26 at risk EG0020 affected17 at risk EG0030 affected9 at risk EG0040 affected37 at risk EG0051 affected21 at risk
Meningitis aseptic	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Septic shock	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Urosepsis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Disease progression	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0021 affected17 at risk EG003
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0021 affected17 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0021 affected17 at risk EG003
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0021 affected17 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Compression fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Foreign body	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Syncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0021 affected17 at risk EG003
Spinal cord compression	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Hepatitis	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0021 affected17 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Haemolysis	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Immune system disorder	Immune system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Delirium	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0021 affected17 at risk EG003
Oedema genital	Reproductive system and breast disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Hypotension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0003 affected8 at risk EG0017 affected26 at risk EG0026 affected17 at risk EG0035 affected9 at risk EG00416 affected37 at risk EG0059 affected21 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0015 affected26 at risk EG0025 affected17 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0019 affected26 at risk EG0023 affected17 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected8 at risk EG0014 affected26 at risk EG0023 affected17 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected8 at risk EG0017 affected26 at risk EG0021 affected17 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0023 affected17 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0013 affected26 at risk EG0021 affected17 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0022 affected17 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0013 affected26 at risk EG0021 affected17 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected8 at risk EG0016 affected26 at risk EG0027 affected17 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected8 at risk EG0015 affected26 at risk EG0024 affected17 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0013 affected26 at risk EG0022 affected17 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0011 affected26 at risk EG0023 affected17 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0012 affected26 at risk EG0022 affected17 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected26 at risk EG0020 affected17 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0013 affected26 at risk EG0020 affected17 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0010 affected26 at risk EG0022 affected17 at risk EG003
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected8 at risk EG00114 affected26 at risk EG0028 affected17 at risk EG003
Oedema peripheral	General disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected8 at risk EG0016 affected26 at risk EG0022 affected17 at risk EG003
Pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0017 affected26 at risk EG0023 affected17 at risk EG003
Chills	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0012 affected26 at risk EG0023 affected17 at risk EG003
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0012 affected26 at risk EG0022 affected17 at risk EG003
Arthralgia	General disorders	MedDRA 19.1	Systematic Assessment	EG0004 affected8 at risk EG0017 affected26 at risk EG0023 affected17 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected8 at risk EG0015 affected26 at risk EG0023 affected17 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0013 affected26 at risk EG0021 affected17 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0013 affected26 at risk EG0023 affected17 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0021 affected17 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected8 at risk EG0012 affected26 at risk EG0021 affected17 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0012 affected26 at risk EG0022 affected17 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0015 affected26 at risk EG0024 affected17 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0018 affected26 at risk EG0024 affected17 at risk EG003
Blood creatinine increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0002 affected8 at risk EG0015 affected26 at risk EG0024 affected17 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0011 affected26 at risk EG0023 affected17 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0013 affected26 at risk EG0024 affected17 at risk EG003
Weight decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0012 affected26 at risk EG0021 affected17 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0004 affected8 at risk EG0018 affected26 at risk EG0024 affected17 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0014 affected26 at risk EG0024 affected17 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0003 affected8 at risk EG0013 affected26 at risk EG0022 affected17 at risk EG003
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0013 affected26 at risk EG0021 affected17 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0012 affected26 at risk EG0021 affected17 at risk EG003
Photophobia	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG00112 affected26 at risk EG0024 affected17 at risk EG003
Vision blurred	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0016 affected26 at risk EG0021 affected17 at risk EG003
Visual impairment	Eye disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0012 affected26 at risk EG0020 affected17 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0004 affected8 at risk EG0017 affected26 at risk EG0025 affected17 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 affected8 at risk EG0017 affected26 at risk EG0021 affected17 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0015 affected26 at risk EG0022 affected17 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0015 affected26 at risk EG0021 affected17 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0014 affected26 at risk EG0020 affected17 at risk EG003
Headache	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0015 affected26 at risk EG0025 affected17 at risk EG003
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0014 affected26 at risk EG0023 affected17 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0004 affected8 at risk EG0014 affected26 at risk EG0024 affected17 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0011 affected26 at risk EG0020 affected17 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0002 affected8 at risk EG0014 affected26 at risk EG0020 affected17 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0015 affected26 at risk EG0022 affected17 at risk EG003
Proteinuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0011 affected26 at risk EG0022 affected17 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0012 affected26 at risk EG0021 affected17 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0001 affected8 at risk EG0010 affected26 at risk EG0022 affected17 at risk EG003
Hypotension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0000 affected8 at risk EG0013 affected26 at risk EG0021 affected17 at risk EG003

ID	Term
D002292	Carcinoma, Renal Cell
D008545	Melanoma
D002289	Carcinoma, Non-Small-Cell Lung

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D007680	Kidney Neoplasms
D014571	Urologic Neoplasms
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D007674	Kidney Diseases
D014570	Urologic Diseases
D052801	Male Urogenital Diseases
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009380	Neoplasms, Nerve Tissue
D018326	Nevi and Melanomas
D012878	Skin Neoplasms
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins