A Study of the Safety and Tolerability of BMS-986183 in Patients With Liver Cancer

A Phase 1/2 Study of BMS-986183 in Subjects With Advanced Hepatocellular Carcinoma

The purpose of this study is to evaluate the safety and tolerability of BMS-986183 in patients with liver cancer.

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: Nivolumab; Biological: BMS-986183

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Local Institution
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Local Institution
• Singapore
  • Singapore, Singapore, 169610
    • Local Institution
• Taiwan
  • Taipei, Taiwan, 10048
    • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Must have advanced liver cancer that cannot be treated with surgery or other local methods
• Liver cancer is confirmed by a microscopic examination of tissue
• Liver disease is classified as 'A' by a standard method called Child-Pugh score
• Daily living abilities are classified as '0 or 1' by a standard method from the Eastern Cooperative Oncology Group (ECOG)
• Women must use contraception

Exclusion Criteria:

• Prior liver transplant
• Increase in blood pressure in some of the veins entering the liver
• Cancer that has spread to the brain or the layers of tissue that cover the brain or spinal cord
• Infection with both hepatitis B and C, both hepatitis D and B, infection with HIV, or other infections
• Disease of the heart or blood vessels around the heart
• Active cancers within the last 2 years
• No more than 2 prior systemic treatments or other investigational agents except PD-1/PD-L1 or Ipilimumab (Part 2)
• Currently on anti-platelet or anti-coagulation therapy
• Radiotherapy within 4 weeks of treatment
• Any major allergies

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dose Escalation Monotherapy	Biological: BMS-986183; specified dose on specified days
EXPERIMENTAL: Dose Expansion Monotherapy	Biological: BMS-986183; specified dose on specified days
EXPERIMENTAL: Dose Escalation Combination Therapy	Biological: Nivolumab; specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: BMS-986183; specified dose on specified days
EXPERIMENTAL: Dose Expansion Combination Therapy	Biological: Nivolumab; specified dose on specified days; Other Names: BMS-936558; Opdivo; Biological: BMS-986183; specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events at Its Worst Grade	Evaluated by comparing the incidence of Adverse Events (AEs) among subjects using their assigned treatment for at least one day.	First dose up to approximately 24 months
Incidence of Serious Adverse Events at Its Worst Grade	Evaluated by comparing the incidence of Serious Adverse Events (SAEs) among subjects using their assigned treatment for at least one day.	First dose up to approximately 24 months
Incidence of Adverse Events Leading to Discontinuation	Evaluated by comparing the incidence of Adverse Events leading to discontinuation among subjects using their assigned treatment for at least one day.	First dose up to approximately 24 months
Incidence of Adverse Events Leading to Death	Evaluated by comparing the incidence of Adverse Events leading to death among subjects using their assigned treatment for at least one day.	First dose up to approximately 24 months
Incidence of Laboratory Test Toxicity Grade Shifting From Baseline		First dose up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response (BOR)	Defined as BOR designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy. CR or PR determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met.	First dose up to approximately 24 months
Overall Response Rate (ORR)	Defined as the total number of subjects whose BOR is either a CR or PR divided by the total number of subjects in the population of interest	First dose up to approximately 24 months
Duration of Response (DoR)	Defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first. For those subjects who remain alive and have not progressed or received subsequent therapy, DoR will be censored on the date of last tumor assessment	First dose up to approximately 24 months
Progression Free Survival (PFS)	Defined as the time from the first dose of study drug to the date of the first objective documentation of tumor progression or death due to any cause. Subjects who did not progress nor died will be censored on the date of their last tumor assessment. Subjects who did not have any on-study tumor assessments will be censored on the date of the first dose of study drug.	First dose up to approximately 24 months
PFS Rate at Week 't'	Defined as the proportion of subjects who remain progression free and surviving at 't' weeks (t=12, 24, 36, etc). The proportion will be calculated by the product-limit method (Kaplan-Meier [K-M] estimate) which takes into account censored data	First dose up to approximately 24 months
Maximum Observed Concentration (Cmax)	To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Cmax	From first does up to approximately 24 months
Time of Maximum Observed Concentration (Tmax)	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Tmax.	First dose up to approximately 24 months
Area Under the Concentration-time Curve From Time 0 to T of the Last Quantifiable Concentration [AUC(0-T)]	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AUC(0-T)]	First does up to appromimately 24 months
Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)]	To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AUC(TAU).	First dose up to approximately 24 months
Concentration at the End of a Dosing Interval (Ctau)	To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by	First dose up to approximately 24 months
Trough Observed Concentration, Including Predose Concentrations and Ctau (Ctrough)	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by (Ctrough)	First dose up to approximately 24 months
Total Body Clearance (CLT)	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by CLT	First dose to approximately 24 months
Apparent Volume of Distribution at Steady-state (Vss)	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Vss	First dose up to approximately 24 months
Volume of Distribution of Terminal Phase (Vz)	(to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Vz.	First dose up to approximately 24 months
Accumulation Index; Ratio of Cmax at Steady-state to Cmax After the First Dose (AI_Cmax)	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_Cmax.	First dose up to approximately 24 months
Accumulation Index; Ratio of Ctau at Steady-state to Ctau After the First Dose (AI_Ctau)	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_Ctau.	First dose up to approximately 24 months
Accumulation Index; Ratio of AUC(TAU) at Steady-state to AUC(TAU) After the First Dose [AI_AUC(TAU)]	To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_AUC(TAU).	First dose up to approximately 24 months
Average Concentration Over a Dosing Interval Calculated by Dividing AUC(TAU) at Steady State by Tau (Css,Ave)	To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Css,avg.	First dose up to approximately 24 months
Terminal Half-life (T-HALF)	to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by T-HALF.	First dose up to approximately 24 months
Changes in QTcF (ΔQTcF) From Baseline	To assess the effect of dosage regimen and exposure [active ADC and unconjugated tubulysin] of BMS-986183 as monotherapy on the QT interval.	Baseline up to approximately 24 months
Incidence of Positive Anti-drug Antibody (ADA)	The immunogenicity of BMS-986183 (as monotherapy and in combination with nivolumab) will be measured by assessment of the presence or absence of specific ADA to BMS-986183. The incidence of positive ADA will be calculated.	First dose up to approximately 24 months

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 23, 2016
• Primary Completion (ACTUAL): January 8, 2018
• Study Completion (ACTUAL): January 8, 2018

Study Registration Dates

• First Submitted: July 7, 2016
• First Submitted That Met QC Criteria: July 8, 2016
• First Posted (ESTIMATE): July 11, 2016

Study Record Updates

• Last Update Posted (ACTUAL): January 30, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA015-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No