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

Advanced Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03792750
• Other study ID #: CA017-076
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 31, 2018
• Est. completion date: December 18, 2020

Study information

• Verified date: February 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: December 18, 2020
• Est. primary completion date: December 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Cancer

Intervention

Drug:
• BMS-986205
Specified Dose on Specified Day

Biological:
• Nivolumab
Specified Dose on Specified Day

Locations

Country	Name	City	State
China	Local Institution	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
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.	From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
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.	From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
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.	From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
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	From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
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)	From first dose to 100 days after last dose of study therapy (up to approximately 2 years)
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.	pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 days 1, 14, Cycle 1 day 1
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.	pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 days 1, 14, Cycle 1 day 1
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.	pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 days 1, 14, Cycle 1 day 1
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.	pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14, Cycle 1 day 1
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.	pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14
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.	pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14
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.	pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 day 14
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.	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
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.	pre-dose, 1, 2, 3, 4, 6, 8 hours post dose on Cycle 0 Day 1 and 2
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.	From first dose up to approximately 2 years
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	From first dose up to approximately 2 years
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.	From first dose up to approximately 2 years
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.	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)
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.	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)
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.	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)

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