Trial Outcomes & Findings for A Study of BMS-986205 Alone and in Combination With Nivolumab in Chinese Patients With Advanced Malignant Solid Tumors (NCT NCT03792750)

NCT ID: NCT03792750

Last Updated: 2022-02-28

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 12 participants
• Primary outcome timeframe: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
• Results posted on: 2022-02-28

Participant Flow

Participant milestones

Measure	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.
Overall Study STARTED	12
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	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.
Overall Study Death	3

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	BMS-986205 in Combination With Nivolumab n=12 Participants 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.
Age, Continuous	55.7 Years STANDARD_DEVIATION 13.7 • n=93 Participants
Sex: Female, Male Female	5 Participants n=93 Participants
Sex: Female, Male Male	7 Participants n=93 Participants
Race/Ethnicity, Customized Chinese	12 Participants n=93 Participants

PRIMARY outcome

Timeframe: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)

Population: All Treated Participants

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.

Outcome measures

Measure

BMS-986205 in Combination With Nivolumab n=12 Participants 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.

The Number of Participants Experiencing Adverse Events (AE)

11 Participants

PRIMARY outcome

Timeframe: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)

Population: All Treated Participants

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.

Outcome measures

Measure

BMS-986205 in Combination With Nivolumab n=12 Participants 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.

The Number of Participants Experiencing Serious Adverse Events (SAE)

3 Participants

PRIMARY outcome

Timeframe: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)

Population: All Treated Participants

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.

Outcome measures

Measure

BMS-986205 in Combination With Nivolumab n=12 Participants 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.

The Number of Participants Experience Adverse Events (AE) Leading to Discontinuation

5 Participants

PRIMARY outcome

Timeframe: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)

Population: All treated Participants

The number of participants who died in each arm during the study to assess the safety and tolerability of BMS-986205.

Outcome measures

Measure

BMS-986205 in Combination With Nivolumab n=12 Participants 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.

Number of Participant Deaths

3 Participants

PRIMARY outcome

Timeframe: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)

Population: All Treated Participants

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

Outcome measures

Measure	BMS-986205 in Combination With Nivolumab n=12 Participants 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.
The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 3XULN	3 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST> 5XULN	2 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST> 10XULN	0 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT OR AST > 20XULN	0 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests TOTAL BILIRUBIN > 1.5XULN	2 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests TOTAL BILIRUBIN > 2XULN	1 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY	0 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS	0 Participants

PRIMARY outcome

Timeframe: From first dose to 100 days after last dose of study therapy (up to approximately 2 years)

Population: All Treated Participants

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)

Outcome measures

Measure	BMS-986205 in Combination With Nivolumab n=12 Participants 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.
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN	4 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN WITH TSH <= ULN AT BASELINE	4 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH >ULN WITH ATLEAST ONE FT3/FT4 TEST VALUE <LLN	2 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH >ULN WITH ALL OTHER FT3/FT4 TEST VALUES >= LLN	4 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH > ULN WITH FT3/FT4 TEST MISSING	0 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN	5 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH <LLN WITH TSH >= LLN AT BASELINE	4 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH <LLN WITH ATLEAST ONE FT3/FT4 TEST VALUE > ULN	0 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH <LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN	5 Participants
The Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests TSH < LLN WITH FT3/FT4 TEST MISSING	0 Participants

PRIMARY outcome

Timeframe: 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

The maximum observes plasma concentration was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab.

Outcome measures

Measure	BMS-986205 in Combination With Nivolumab n=12 Participants 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.
(Cmax) Maximum Observed Plasma Concentration C0D1	596.0 ng/mL Geometric Coefficient of Variation 44.138
(Cmax) Maximum Observed Plasma Concentration C0D14	701.9 ng/mL Geometric Coefficient of Variation 24.870
(Cmax) Maximum Observed Plasma Concentration C1D1	781.0 ng/mL Geometric Coefficient of Variation 18.933

PRIMARY outcome

Timeframe: 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

The time of maximum observed plasma concentration was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab.

Outcome measures

Measure	BMS-986205 in Combination With Nivolumab n=12 Participants 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.
(Tmax) Time of Maximum Observed Plasma Concentration C0D1	2.5 hours Interval 1.0 to 3.0
(Tmax) Time of Maximum Observed Plasma Concentration C0D14	2.5 hours Interval 2.0 to 4.0
(Tmax) Time of Maximum Observed Plasma Concentration C1D1	2.5 hours Interval 1.1 to 4.0

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Measure	BMS-986205 in Combination With Nivolumab n=12 Participants 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.
(AUC(TAU)) Area Under the Concentration-time Curve in One Dosing Interval C0D1	3380.8 ng*h/mL Geometric Coefficient of Variation 34.754
(AUC(TAU)) Area Under the Concentration-time Curve in One Dosing Interval C0D14	6048.3 ng*h/mL Geometric Coefficient of Variation 38.830
(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 outcome

Timeframe: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14, Cycle 1 day 1

Population: Evaluable PK Population

The apparent total body clearance was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab.

Outcome measures

Measure	BMS-986205 in Combination With Nivolumab n=12 Participants 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.
(CLT/F) Apparent Total Body Clearance CYCLE0 DAY14	16.5 L/h Geometric Coefficient of Variation 38.830
(CLT/F) Apparent Total Body Clearance CYCLE1 DAY1	16.9 L/h Geometric Coefficient of Variation 32.572

PRIMARY outcome

Timeframe: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14

Population: Evaluable PK Population

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.

Outcome measures

Measure

BMS-986205 in Combination With Nivolumab n=11 Participants 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.

(T-HALF (Eff, AUC)) Effective Elimination Half-life

22.9 Hours Standard Deviation 9.40

PRIMARY outcome

Timeframe: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14

Population: Evaluable PK Population

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.

Outcome measures

Measure

BMS-986205 in Combination With Nivolumab n=12 Participants 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.

(AI_CMAX) Accumulation Index

1.2 ng/mL Geometric Coefficient of Variation 42.479

PRIMARY outcome

Timeframe: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14

Population: Evaluable PK Population

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.

Outcome measures

Measure

BMS-986205 in Combination With Nivolumab n=12 Participants 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.

(AI_AUC ) Accumulation Index

1.8 ng*h/mL Geometric Coefficient of Variation 32.866

PRIMARY outcome

Timeframe: 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

The trough observed plasma concentration was collected to characterize the pharmacokinetics of BMS-986205 administered alone and in combination with nivolumab.

Outcome measures

Measure	BMS-986205 in Combination With Nivolumab n=12 Participants 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.
(Ctrough) Trough Observed Plasma Concentration Cycle0 Day2	51.2 ug/mL Geometric Coefficient of Variation 35.255
(Ctrough) Trough Observed Plasma Concentration Cycle0 Day8	117.4 ug/mL Geometric Coefficient of Variation 44.282
(Ctrough) Trough Observed Plasma Concentration Cycle0 Day14	154.9 ug/mL Geometric Coefficient of Variation 51.005
(Ctrough) Trough Observed Plasma Concentration Cycle1 Day1	141.5 ug/mL Geometric Coefficient of Variation 60.276
(Ctrough) Trough Observed Plasma Concentration Cycle1 Day2	150.2 ug/mL Geometric Coefficient of Variation 46.971
(Ctrough) Trough Observed Plasma Concentration CYCLE3 DAY1	161.3 ug/mL Geometric Coefficient of Variation 97.305
(Ctrough) Trough Observed Plasma Concentration CYCLE5 DAY1	239.2 ug/mL Geometric Coefficient of Variation 38.883
(Ctrough) Trough Observed Plasma Concentration CYCLE9 DAY1	144.0 ug/mL Geometric Coefficient of Variation 64.086
(Ctrough) Trough Observed Plasma Concentration CYCLE13 DAY1	134.0 ug/mL Geometric Coefficient of Variation NA Coefficient of Variation is not evaluable for only 1 participant
(Ctrough) Trough Observed Plasma Concentration CYCLE17 DAY1	3.2 ug/mL Geometric Coefficient of Variation NA Coefficient of Variation is not evaluable for only 1 participant

PRIMARY outcome

Timeframe: pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 Day 1 and 2

Population: Evaluable PK Population

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose up to approximately 2 years

Population: All Treated Participants

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.

Outcome measures

Measure

BMS-986205 in Combination With Nivolumab n=12 Participants 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.

Objective Response Rate (ORR)

1 Participants

SECONDARY outcome

Timeframe: From first dose up to approximately 2 years

Population: All treated Participants

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

Outcome measures

Measure	BMS-986205 in Combination With Nivolumab n=12 Participants 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.
Best Overall Response (BOR) COMPLETE RESPONSE (CR)	0 Participants
Best Overall Response (BOR) PARTIAL RESPONSE (PR)	1 Participants
Best Overall Response (BOR) STABLE DISEASE (SD)	5 Participants
Best Overall Response (BOR) PROGRESSIVE DISEASE (PD)	5 Participants
Best Overall Response (BOR) UNABLE TO DETERMINE (UTD)	1 Participants

SECONDARY outcome

Timeframe: From first dose up to approximately 2 years

Population: All treated participants with a BOR of CR or PR

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.

Outcome measures

Measure

BMS-986205 in Combination With Nivolumab n=1 Participants 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.

Duration of Response (DOR)

72 Weeks

SECONDARY outcome

Timeframe: 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

Measurement of kynurenine levels were assessed to characterize the pharmacodynamic activity of BMS-986205 administered alone and in combination with nivolumab.

Outcome measures

Measure	BMS-986205 in Combination With Nivolumab n=12 Participants 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.
Measurement of Serum Kynurenine Levels BASELINE	189.6 ng/mL Standard Deviation 64.46
Measurement of Serum Kynurenine Levels CYCLE 1 D1 6 HOUR POST-DOSE	150.8 ng/mL Standard Deviation 45.39
Measurement of Serum Kynurenine Levels CYCLE 1 D2	180.6 ng/mL Standard Deviation 49.33
Measurement of Serum Kynurenine Levels CYCLE 3 D1	273.0 ng/mL Standard Deviation NA SD is not applicable for 1 evaluable participant
Measurement of Serum Kynurenine Levels CYCLE 6 D1	111.0 ng/mL Standard Deviation NA SD is not applicable for 1 evaluable participant
Measurement of Serum Kynurenine Levels CYCLE 8 D1	124.0 ng/mL Standard Deviation NA SD is not applicable for 1 evaluable participant
Measurement of Serum Kynurenine Levels END OF TREATMENT	198.5 ng/mL Standard Deviation 50.2

SECONDARY outcome

Timeframe: 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

Measurement of tryptophan levels were assessed to characterize the pharmacodynamic activity of BMS-986205 administered alone and in combination with nivolumab.

Outcome measures

Measure	BMS-986205 in Combination With Nivolumab n=12 Participants 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.
Measurement of Tryptophan Levels BASELINE	13445.8 ng/mL Standard Deviation 2671.18
Measurement of Tryptophan Levels CYCLE 1 D1 6 HOUR POST-DOSE	14528.3 ng/mL Standard Deviation 2461.75
Measurement of Tryptophan Levels CYCLE 1 D2	12508.3 ng/mL Standard Deviation 2461.30
Measurement of Tryptophan Levels CYCLE 3 D1	17900.0 ng/mL Standard Deviation NA SD is not applicable for 1 evaluable participant
Measurement of Tryptophan Levels CYCLE 6 D1	13200.0 ng/mL Standard Deviation NA SD is not applicable for 1 evaluable participant
Measurement of Tryptophan Levels CYCLE 8 D1	13200.0 ng/mL Standard Deviation NA SD is not applicable for 1 evaluable participant
Measurement of Tryptophan Levels END OF TREATMENT	14200.0 ng/mL Standard Deviation 3394.11

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	BMS-986205 in Combination With Nivolumab n=7 Participants 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.
Number of Participants With Anti-drug Antibodies (ADA) to Nivolumab BASELINE ADA POSITIVE	1 Participants
Number of Participants With Anti-drug Antibodies (ADA) to Nivolumab ADA POSITIVE	0 Participants
Number of Participants With Anti-drug Antibodies (ADA) to Nivolumab NEUTRALIZING POSITIVE	1 Participants
Number of Participants With Anti-drug Antibodies (ADA) to Nivolumab ADA NEGATIVE	7 Participants

Adverse Events

BMS-986205 in Combination With Nivolumab

Serious events: 3 serious events

Other events: 11 other events

Deaths: 3 deaths

Serious adverse events

Measure	BMS-986205 in Combination With Nivolumab n=12 participants at risk 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.
Infections and infestations Tuberculosis	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	16.7% 2/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Renal and urinary disorders Acute kidney injury	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Respiratory, thoracic and mediastinal disorders Pneumonitis	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)

Other adverse events

Measure	BMS-986205 in Combination With Nivolumab n=12 participants at risk 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.
Blood and lymphatic system disorders Anaemia	75.0% 9/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Blood and lymphatic system disorders Leukocytosis	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Blood and lymphatic system disorders Leukopenia	50.0% 6/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Blood and lymphatic system disorders Neutropenia	16.7% 2/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Blood and lymphatic system disorders Thrombocytopenia	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Endocrine disorders Hypothyroidism	25.0% 3/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Eye disorders Uveitis	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Gastrointestinal disorders Abdominal distension	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Gastrointestinal disorders Constipation	25.0% 3/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Gastrointestinal disorders Diarrhoea	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Gastrointestinal disorders Haematochezia	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Gastrointestinal disorders Vomiting	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
General disorders Malaise	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
General disorders Oedema peripheral	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
General disorders Pyrexia	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Infections and infestations Conjunctivitis	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Infections and infestations Pneumonia	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Infections and infestations Upper respiratory tract infection	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Alanine aminotransferase increased	58.3% 7/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Aspartate aminotransferase increased	66.7% 8/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Blood alkaline phosphatase increased	25.0% 3/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Blood bilirubin increased	33.3% 4/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Blood creatine phosphokinase increased	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Blood creatinine increased	16.7% 2/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Blood lactate dehydrogenase increased	16.7% 2/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Blood thyroid stimulating hormone decreased	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Blood thyroid stimulating hormone increased	16.7% 2/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations C-reactive protein increased	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Gamma-glutamyltransferase increased	16.7% 2/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Myoglobin blood increased	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Neutrophil count decreased	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Neutrophil count increased	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Platelet count decreased	25.0% 3/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Thyroxine increased	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations Weight decreased	16.7% 2/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations White blood cell count decreased	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Investigations White blood cell count increased	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Metabolism and nutrition disorders Decreased appetite	16.7% 2/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Metabolism and nutrition disorders Hypoalbuminaemia	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	25.0% 3/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Nervous system disorders Dizziness	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Psychiatric disorders Insomnia	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Renal and urinary disorders Acute kidney injury	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Respiratory, thoracic and mediastinal disorders Cough	16.7% 2/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 2/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Respiratory, thoracic and mediastinal disorders Haemoptysis	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Respiratory, thoracic and mediastinal disorders Immune-mediated lung disease	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Respiratory, thoracic and mediastinal disorders Pneumonitis	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Skin and subcutaneous tissue disorders Leukoderma	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Skin and subcutaneous tissue disorders Rash	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)
Vascular disorders Hypertension	8.3% 1/12 • First dose and 100 days after last dose of study therapy (Up to approximately 2 years)

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please email

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
• Publication restrictions are in place

Restriction type: OTHER