A Study of BMS-986205 Alone and in Combination With Nivolumab in Chinese Patients With Advanced Malignant Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1/2 Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of BMS-986205 Alone and in Combination With Nivolumab in Chinese Patients With Advanced Malignant Solid Tumors

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: BMS-986205
* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have histologic or cytological confirmation of a solid tumor that is advanced with measureable disease per RECIST v1.1 Participants must have received, and then progressed or been intolerant to at least one standard treatment regimen in the advanced or metastatic setting Participants must have an ECOG performance status of less than or equal to 1 Participants must have at least 1 lesion with measurable disease as defined by RECIST Version 1.1 Exclusion Criteria: Participants must not have suspected, known, or progressive CNS metastases, have untreated CNS metastases, or have the CNS as the only site of disease Participants with prior exposure to anti PD-1 or anti-PDL1 therapy Participants must not have a history of allergy to any of the study treatment components

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm A<br>2 week BMS-986205 monotherapy lead in followed by BMS-986205 + Nivo combination therapy | Drug: BMS-986205<br>* Specified Dose on Specified Day<br>Biological: Nivolumab<br>* Specified Dose on Specified Day<br>* Other names: BMS-936558;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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 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 | 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) | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 Day 1 and 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 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. | 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. | 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. | 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. | 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) |