Advanced Cancer
Conditions
Brief summary
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.
Interventions
DRUGBMS-986205
Specified Dose on Specified Day
BIOLOGICALNivolumab
Specified Dose on Specified Day
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| (percentUR24) Percent Urinary Recovery Over 24 Hours | pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 Day 1 and 2 | 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. |
| (AUC(TAU)) Area Under the Concentration-time Curve in One Dosing Interval | pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 days 1, 14, Cycle 1 day 1 | 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. |
| (CLT/F) Apparent Total Body Clearance | pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14, Cycle 1 day 1 | The apparent total body clearance was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab. |
| (T-HALF (Eff, AUC)) Effective Elimination Half-life | pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14 | 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. |
| (AI_CMAX) Accumulation Index | pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14 | 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. |
| (AI_AUC ) Accumulation Index | pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14 | 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. |
| (Ctrough) Trough Observed Plasma Concentration | 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 | The trough observed plasma concentration was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab. |
| The Number of Participants Experiencing Adverse Events (AE) | From first dose to 100 days after last dose of study therapy (up to approximately 2 years) | 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. |
| The Number of Participants Experiencing Serious Adverse Events (SAE) | 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 (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. |
| The Number of Participants Experience Adverse Events (AE) Leading to Discontinuation | From first dose to 100 days after last dose of study therapy (up to approximately 2 years) | 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. |
| Number of Participant Deaths | From first dose to 100 days after last dose of study therapy (up to approximately 2 years) | The number of participants who died in each arm during the study to assess the safety and tolerability of BMS-986205. |
| The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | From first dose to 100 days after last dose of study therapy (up to approximately 2 years) | 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 |
| The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | From first dose to 100 days after last dose of study therapy (up to approximately 2 years) | 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) |
| (Cmax) Maximum Observed Plasma Concentration | pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 days 1, 14, Cycle 1 day 1 | The maximum observes plasma concentration was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab. |
| (Tmax) Time of Maximum Observed Plasma Concentration | pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 days 1, 14, Cycle 1 day 1 | The time of maximum observed plasma concentration was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (BOR) | From first dose up to approximately 2 years | 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 |
| Duration of Response (DOR) | From first dose up to approximately 2 years | 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. |
| Measurement of Serum Kynurenine Levels | 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 kynurenine levels were assessed to characterize the pharmacodynamic activity of BMS-986205 administered alone and in combination with nivolumab. |
| Measurement of Tryptophan Levels | 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 were assessed to characterize the pharmacodynamic activity of BMS-986205 administered alone and in combination with nivolumab. |
| Number of Participants With Anti-drug Antibodies (ADA) to Nivolumab | 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) | 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. |
| Objective Response Rate (ORR) | From first dose up to approximately 2 years | 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. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BMS-986205 in Combination With Nivolumab Study treatment starts with a monotherapy therapy 2-week lead-in treatment (Cycle 0) consisting of a single oral daily dose of 100 mg BMS-986205. Followed by combination therapy cycles comprised of an oral daily dose of 100mg BMS-986205 and one dose of 480mg nivolumab administered intravenously Q4W on Day 1 of each treatment cycle up to 12 cycles. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
Baseline characteristics
| Characteristic | BMS-986205 in Combination With Nivolumab |
|---|---|
| Age, Continuous | 55.7 Years STANDARD_DEVIATION 13.7 |
| Race/Ethnicity, Customized Chinese | 12 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 12 |
| other Total, other adverse events | 11 / 12 |
| serious Total, serious adverse events | 3 / 12 |
Outcome results
Primary
(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
Population: Evaluable PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | (AI_AUC ) Accumulation Index | 1.8 ng*h/mL | Geometric Coefficient of Variation 32.866 |
Primary
(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
Population: Evaluable PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | (AI_CMAX) Accumulation Index | 1.2 ng/mL | Geometric Coefficient of Variation 42.479 |
Primary
(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
Population: Evaluable PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | (AUC(TAU)) Area Under the Concentration-time Curve in One Dosing Interval | C0D1 | 3380.8 ng*h/mL | Geometric Coefficient of Variation 34.754 |
| BMS-986205 in Combination With Nivolumab | (AUC(TAU)) Area Under the Concentration-time Curve in One Dosing Interval | C0D14 | 6048.3 ng*h/mL | Geometric Coefficient of Variation 38.83 |
| BMS-986205 in Combination With Nivolumab | (AUC(TAU)) Area Under the Concentration-time Curve in One Dosing Interval | C1D1 | 5922.3 ng*h/mL | Geometric Coefficient of Variation 32.572 |
Primary
(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
Population: Evaluable PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | (CLT/F) Apparent Total Body Clearance | CYCLE0 DAY14 | 16.5 L/h | Geometric Coefficient of Variation 38.83 |
| BMS-986205 in Combination With Nivolumab | (CLT/F) Apparent Total Body Clearance | CYCLE1 DAY1 | 16.9 L/h | Geometric Coefficient of Variation 32.572 |
Primary
(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
Population: Evaluable PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | (Cmax) Maximum Observed Plasma Concentration | C0D1 | 596.0 ng/mL | Geometric Coefficient of Variation 44.138 |
| BMS-986205 in Combination With Nivolumab | (Cmax) Maximum Observed Plasma Concentration | C0D14 | 701.9 ng/mL | Geometric Coefficient of Variation 24.87 |
| BMS-986205 in Combination With Nivolumab | (Cmax) Maximum Observed Plasma Concentration | C1D1 | 781.0 ng/mL | Geometric Coefficient of Variation 18.933 |
Primary
(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
Population: Evaluable PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | (Ctrough) Trough Observed Plasma Concentration | Cycle0 Day2 | 51.2 ug/mL | Geometric Coefficient of Variation 35.255 |
| BMS-986205 in Combination With Nivolumab | (Ctrough) Trough Observed Plasma Concentration | Cycle0 Day8 | 117.4 ug/mL | Geometric Coefficient of Variation 44.282 |
| BMS-986205 in Combination With Nivolumab | (Ctrough) Trough Observed Plasma Concentration | Cycle0 Day14 | 154.9 ug/mL | Geometric Coefficient of Variation 51.005 |
| BMS-986205 in Combination With Nivolumab | (Ctrough) Trough Observed Plasma Concentration | Cycle1 Day1 | 141.5 ug/mL | Geometric Coefficient of Variation 60.276 |
| BMS-986205 in Combination With Nivolumab | (Ctrough) Trough Observed Plasma Concentration | Cycle1 Day2 | 150.2 ug/mL | Geometric Coefficient of Variation 46.971 |
| BMS-986205 in Combination With Nivolumab | (Ctrough) Trough Observed Plasma Concentration | CYCLE3 DAY1 | 161.3 ug/mL | Geometric Coefficient of Variation 97.305 |
| BMS-986205 in Combination With Nivolumab | (Ctrough) Trough Observed Plasma Concentration | CYCLE5 DAY1 | 239.2 ug/mL | Geometric Coefficient of Variation 38.883 |
| BMS-986205 in Combination With Nivolumab | (Ctrough) Trough Observed Plasma Concentration | CYCLE9 DAY1 | 144.0 ug/mL | Geometric Coefficient of Variation 64.086 |
| BMS-986205 in Combination With Nivolumab | (Ctrough) Trough Observed Plasma Concentration | CYCLE13 DAY1 | 134.0 ug/mL | — |
| BMS-986205 in Combination With Nivolumab | (Ctrough) Trough Observed Plasma Concentration | CYCLE17 DAY1 | 3.2 ug/mL | — |
Primary
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)
Population: All treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS-986205 in Combination With Nivolumab | Number of Participant Deaths | 3 Participants |
Primary
(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
Population: Evaluable PK Population
Primary
(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
Population: Evaluable PK Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | (T-HALF (Eff, AUC)) Effective Elimination Half-life | 22.9 Hours | Standard Deviation 9.4 |
Primary
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)
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experience Adverse Events (AE) Leading to Discontinuation | 5 Participants |
Primary
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)
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Adverse Events (AE) | 11 Participants |
Primary
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)
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY | 0 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 3XULN | 3 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST> 5XULN | 2 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST> 10XULN | 0 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 20XULN | 0 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | TOTAL BILIRUBIN > 1.5XULN | 2 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | TOTAL BILIRUBIN > 2XULN | 1 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS | 0 Participants |
Primary
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)
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN | 5 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN | 4 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH TSH <= ULN AT BASELINE | 4 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN | 2 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN | 4 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH FT3/FT4 TEST MISSING | 0 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 5 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH <LLN WITH TSH >= LLN AT BASELINE | 4 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN | 0 Participants |
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH FT3/FT4 TEST MISSING | 0 Participants |
Primary
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)
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS-986205 in Combination With Nivolumab | The Number of Participants Experiencing Serious Adverse Events (SAE) | 3 Participants |
Primary
(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
Population: Evaluable PK Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | (Tmax) Time of Maximum Observed Plasma Concentration | C0D1 | 2.5 hours |
| BMS-986205 in Combination With Nivolumab | (Tmax) Time of Maximum Observed Plasma Concentration | C0D14 | 2.5 hours |
| BMS-986205 in Combination With Nivolumab | (Tmax) Time of Maximum Observed Plasma Concentration | C1D1 | 2.5 hours |
Secondary
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
Population: All treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | Best Overall Response (BOR) | COMPLETE RESPONSE (CR) | 0 Participants |
| BMS-986205 in Combination With Nivolumab | Best Overall Response (BOR) | PARTIAL RESPONSE (PR) | 1 Participants |
| BMS-986205 in Combination With Nivolumab | Best Overall Response (BOR) | STABLE DISEASE (SD) | 5 Participants |
| BMS-986205 in Combination With Nivolumab | Best Overall Response (BOR) | PROGRESSIVE DISEASE (PD) | 5 Participants |
| BMS-986205 in Combination With Nivolumab | Best Overall Response (BOR) | UNABLE TO DETERMINE (UTD) | 1 Participants |
Secondary
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
Population: All treated participants with a BOR of CR or PR
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986205 in Combination With Nivolumab | Duration of Response (DOR) | 72 Weeks |
Secondary
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)
Population: All Treated Participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | Measurement of Serum Kynurenine Levels | BASELINE | 189.6 ng/mL | Standard Deviation 64.46 |
| BMS-986205 in Combination With Nivolumab | Measurement of Serum Kynurenine Levels | CYCLE 1 D1 6 HOUR POST-DOSE | 150.8 ng/mL | Standard Deviation 45.39 |
| BMS-986205 in Combination With Nivolumab | Measurement of Serum Kynurenine Levels | CYCLE 1 D2 | 180.6 ng/mL | Standard Deviation 49.33 |
| BMS-986205 in Combination With Nivolumab | Measurement of Serum Kynurenine Levels | CYCLE 3 D1 | 273.0 ng/mL | — |
| BMS-986205 in Combination With Nivolumab | Measurement of Serum Kynurenine Levels | CYCLE 6 D1 | 111.0 ng/mL | — |
| BMS-986205 in Combination With Nivolumab | Measurement of Serum Kynurenine Levels | CYCLE 8 D1 | 124.0 ng/mL | — |
| BMS-986205 in Combination With Nivolumab | Measurement of Serum Kynurenine Levels | END OF TREATMENT | 198.5 ng/mL | Standard Deviation 50.2 |
Secondary
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)
Population: All Treated Participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | Measurement of Tryptophan Levels | CYCLE 1 D2 | 12508.3 ng/mL | Standard Deviation 2461.3 |
| BMS-986205 in Combination With Nivolumab | Measurement of Tryptophan Levels | BASELINE | 13445.8 ng/mL | Standard Deviation 2671.18 |
| BMS-986205 in Combination With Nivolumab | Measurement of Tryptophan Levels | CYCLE 1 D1 6 HOUR POST-DOSE | 14528.3 ng/mL | Standard Deviation 2461.75 |
| BMS-986205 in Combination With Nivolumab | Measurement of Tryptophan Levels | CYCLE 3 D1 | 17900.0 ng/mL | — |
| BMS-986205 in Combination With Nivolumab | Measurement of Tryptophan Levels | CYCLE 6 D1 | 13200.0 ng/mL | — |
| BMS-986205 in Combination With Nivolumab | Measurement of Tryptophan Levels | CYCLE 8 D1 | 13200.0 ng/mL | — |
| BMS-986205 in Combination With Nivolumab | Measurement of Tryptophan Levels | END OF TREATMENT | 14200.0 ng/mL | Standard Deviation 3394.11 |
Secondary
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)
Population: All Nivolumab Treated Subjects with Baseline and at Least One Post-Baseline Immunogenicity Assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986205 in Combination With Nivolumab | Number of Participants With Anti-drug Antibodies (ADA) to Nivolumab | ADA POSITIVE | 0 Participants |
| BMS-986205 in Combination With Nivolumab | Number of Participants With Anti-drug Antibodies (ADA) to Nivolumab | BASELINE ADA POSITIVE | 1 Participants |
| BMS-986205 in Combination With Nivolumab | Number of Participants With Anti-drug Antibodies (ADA) to Nivolumab | NEUTRALIZING POSITIVE | 1 Participants |
| BMS-986205 in Combination With Nivolumab | Number of Participants With Anti-drug Antibodies (ADA) to Nivolumab | ADA NEGATIVE | 7 Participants |
Secondary
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
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS-986205 in Combination With Nivolumab | Objective Response Rate (ORR) | 1 Participants |