The purpose of this study is to determine safety and effectiveness of experimental medication BMS-986205 in combination with Nivolumab in patients with cancers that are advanced or have spread.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Specified Dose on Specified Day
Specified Dose on Specified Day
Local Institution
Hangzhou, Zhejiang, China
The Number of Participants Experiencing Adverse Events (AE)
The number of participants experiencing adverse events (AEs) to assess the safety and tolerability of BMS-986205. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
The Number of Participants Experiencing Serious Adverse Events (SAE)
The number of participants experiencing serious adverse events (SAEs) to assess the safety and tolerability of BMS-986205 Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time frame: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
The Number of Participants Experience Adverse Events (AE) Leading to Discontinuation
The number of participants experiencing adverse events (AEs) leading to discontinuation to assess the safety and tolerability of BMS-986205 An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
Number of Participant Deaths
The number of participants who died in each arm during the study to assess the safety and tolerability of BMS-986205.
Time frame: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
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The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests
The number of participants with clinical laboratory test abnormalities in specific liver tests based on US conventional units to assess the safety and tolerability of BMS-986205. The number of participants with the following laboratory abnormalities will be summarized: ALT or AST \> 3 x ULN, \> 5 x ULN, \> 10 x ULN and \> 20 x ULN Total bilirubin \> 1.5 x ULN and 2 x ULN Concurrent (within 1 day) ALT or AST \> 3 x ULN with total bilirubin \> 2 x ULN Concurrent (within 30 days) ALT or AST \> 3 x ULN with total bilirubin \> 2 x ULN
Time frame: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests
The number of participants with clinical laboratory test abnormalities based on US conventional units to assess the safety and tolerability of BMS-986205. The number of subjects with the following laboratory abnormalities will be summarized: TSH \> ULN WITH TSH \<= ULN AT BASELINE WITH AT LEAST ONE FT3/FT4 TEST VALUE \< LLN (Within a 2-week window after the abnormal TSH test date) WITH ALL OTHER FT3/FT4 TEST VALUES \>= LLN (Within a 2-week window after the abnormal TSH test date) WITH FT3/FT4 TEST MISSING (Within a 2-week window after the abnormal TSH test date) TSH \< LLN WITH TSH \>= LLN AT BASELINE WITH AT LEAST ONE FT3/FT4 TEST VALUE \> ULN (Within a 2-week window after the abnormal TSH test date) WITH ALL OTHER FT3/FT4 TEST VALUES \<= ULN (Within a 2-week window after the abnormal TSH test date) WITH FT3/FT4 TEST MISSING (Within a 2-week window after the abnormal TSH test date)
Time frame: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
(Cmax) Maximum Observed Plasma Concentration
The maximum observes plasma concentration was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab.
Time frame: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 days 1, 14, Cycle 1 day 1
(Tmax) Time of Maximum Observed Plasma Concentration
The time of maximum observed plasma concentration was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab.
Time frame: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 days 1, 14, Cycle 1 day 1
(AUC(TAU)) Area Under the Concentration-time Curve in One Dosing Interval
The area under the concentration-time curve in one dosing interval was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab.
Time frame: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 days 1, 14, Cycle 1 day 1
(CLT/F) Apparent Total Body Clearance
The apparent total body clearance was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab.
Time frame: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14, Cycle 1 day 1
(T-HALF (Eff, AUC)) Effective Elimination Half-life
The effective elimination half-life was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab. T-HALF (eff, AUC) explains the degree of AUC accumulation observed.
Time frame: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14
(AI_CMAX) Accumulation Index
The accumulation index was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab. AI is calculated based on ratio of Cmax at steady state to after the first dose.
Time frame: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14
(AI_AUC ) Accumulation Index
The accumulation index was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab. AI is calculated based on ratio of AUC(TAU) at steady state to after the first dose.
Time frame: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14
(Ctrough) Trough Observed Plasma Concentration
The trough observed plasma concentration was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab.
Time frame: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 2, 8, 14, Cycle 1 day 1, 2, Cycle 3, 5, 9, 13, and 17 day 1
(percentUR24) Percent Urinary Recovery Over 24 Hours
The percent urinary recovery over 24 hours was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab. BMS-986205 had minimal evaluable concentration in urine to derive the parameter.
Time frame: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 Day 1 and 2
Objective Response Rate (ORR)
ORR is defined as the total number of participants whose best overall response (BOR) is either a completer response (CR) or partial response (PR) divided by the total number of participants in the population of interest. Assessed per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 by investigator BOR is defined as the best response designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy.
Time frame: From first dose up to approximately 2 years
Best Overall Response (BOR)
BOR defined as the best response designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy. Assessed per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 by investigator
Time frame: From first dose up to approximately 2 years
Duration of Response (DOR)
Duration of Response (DOR) is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first. Assessed per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 by investigator.
Time frame: From first dose up to approximately 2 years
Measurement of Serum Kynurenine Levels
Measurement of kynurenine levels were assessed to characterize the pharmacodynamic activity of BMS-986205 administered alone and in combination with nivolumab.
Time frame: Baseline, pre-dose (C1D1), 6 hours post dose (C1D1), pre-dose (C1D2), and at disease progression (actually collected on C3D1, C6D1, C8D1, and end of treatment-an average of 12 cycles)
Measurement of Tryptophan Levels
Measurement of tryptophan levels were assessed to characterize the pharmacodynamic activity of BMS-986205 administered alone and in combination with nivolumab.
Time frame: Baseline, pre-dose (C1D1), 6 hours post dose (C1D1), pre-dose (C1D2), and at disease progression (actually collected on C3D1, C6D1, C8D1, and end of treatment-an average of 12 cycles)
Number of Participants With Anti-drug Antibodies (ADA) to Nivolumab
The number of participants with positive or negative anti-drug antibodies (ADA) to nivolumab was collected to characterize the immunogenicity of nivolumab when administered in combination with BMS-986205. Baseline ADA Positive: A subject with baseline ADA-positive sample. ADA Positive: A subject with at least one ADA-positive sample relative to baseline. Neutralizing Positive: At least one ADA-positive sample with neutralizing antibodies detected post-baseline ADA Negative: A subject with no ADA-positive sample after initiation of treatment.
Time frame: Baseline, pre-dose (C1D1, C3D1, every 4 Cycles from C5D1), end of treatment - an average of 12 cycles, and follow up. (up to approximately 2 years)