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

NCT03792750 | Completed Phase 1 Results FDA Drug

• 1 other identifier: CA017-076
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Cancer

Outcome Measures

Primary Outcomes (15)

• 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 Outcomes (6)

• Objective Response Rate (ORR)

  From first dose up to approximately 2 years

• Best Overall Response (BOR)

  From first dose up to approximately 2 years

• Duration of Response (DOR)

  From first dose up to approximately 2 years

• 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 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)

Study Arms (1)

Experimental Arm A

EXPERIMENTAL

2 week BMS-986205 monotherapy lead in followed by BMS-986205 + Nivo combination therapy

Drug: BMS-986205; Biological: Nivolumab

Interventions

BMS-986205 DRUG

Specified Dose on Specified Day

Experimental Arm A

Nivolumab BIOLOGICAL

Specified Dose on Specified Day

Also known as: BMS-936558

Experimental Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (1)

Local Institution

Hangzhou, Zhejiang, 310016, China

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

MeSH Terms

Interventions

linrodostat; Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2019
• First Posted: January 3, 2019
• Study Start: December 31, 2018
• Primary Completion: December 18, 2020
• Study Completion: December 18, 2020
• Last Updated: February 28, 2022
• Results First Posted: February 28, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)