A Study of the Safety and Tolerability of BMS-986183 in Patients With Liver Cancer
- Conditions
- Hepatocellular Carcinoma
- Interventions
- Biological: BMS-986183Biological: Nivolumab
- Registration Number
- NCT02828124
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to evaluate the safety and tolerability of BMS-986183 in patients with liver cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 25
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Escalation Combination Therapy BMS-986183 - Dose Escalation Monotherapy BMS-986183 - Dose Expansion Monotherapy BMS-986183 - Dose Escalation Combination Therapy Nivolumab - Dose Expansion Combination Therapy Nivolumab - Dose Expansion Combination Therapy BMS-986183 -
- Primary Outcome Measures
Name Time Method Incidence of Adverse Events at Its Worst Grade First dose up to approximately 24 months Evaluated by comparing the incidence of Adverse Events (AEs) among subjects using their assigned treatment for at least one day.
Incidence of Adverse Events Leading to Discontinuation First dose up to approximately 24 months Evaluated by comparing the incidence of Adverse Events leading to discontinuation among subjects using their assigned treatment for at least one day.
Incidence of Serious Adverse Events at Its Worst Grade First dose up to approximately 24 months Evaluated by comparing the incidence of Serious Adverse Events (SAEs) among subjects using their assigned treatment for at least one day.
Incidence of Adverse Events Leading to Death First dose up to approximately 24 months Evaluated by comparing the incidence of Adverse Events leading to death among subjects using their assigned treatment for at least one day.
Incidence of Laboratory Test Toxicity Grade Shifting From Baseline First dose up to approximately 24 months
- Secondary Outcome Measures
Name Time Method Overall Response Rate (ORR) First dose up to approximately 24 months 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
Time of Maximum Observed Concentration (Tmax) First dose up to approximately 24 months 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.
Area Under the Concentration-time Curve From Time 0 to T of the Last Quantifiable Concentration [AUC(0-T)] First does up to appromimately 24 months 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)\]
Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)] First dose up to approximately 24 months 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).
Best Overall Response (BOR) First dose up to approximately 24 months 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.
Duration of Response (DoR) First dose up to approximately 24 months 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
Progression Free Survival (PFS) First dose up to approximately 24 months 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.
PFS Rate at Week 't' First dose up to approximately 24 months 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
Maximum Observed Concentration (Cmax) From first does up to approximately 24 months 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
Trough Observed Concentration, Including Predose Concentrations and Ctau (Ctrough) First dose up to approximately 24 months 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)
Total Body Clearance (CLT) First dose to approximately 24 months 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
Concentration at the End of a Dosing Interval (Ctau) First dose up to approximately 24 months 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
Apparent Volume of Distribution at Steady-state (Vss) First dose up to approximately 24 months 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
Volume of Distribution of Terminal Phase (Vz) First dose up to approximately 24 months (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.
Accumulation Index; Ratio of Cmax at Steady-state to Cmax After the First Dose (AI_Cmax) First dose up to approximately 24 months 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.
Accumulation Index; Ratio of Ctau at Steady-state to Ctau After the First Dose (AI_Ctau) First dose up to approximately 24 months 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.
Accumulation Index; Ratio of AUC(TAU) at Steady-state to AUC(TAU) After the First Dose [AI_AUC(TAU)] First dose up to approximately 24 months 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).
Average Concentration Over a Dosing Interval Calculated by Dividing AUC(TAU) at Steady State by Tau (Css,Ave) First dose up to approximately 24 months 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.
Terminal Half-life (T-HALF) First dose up to approximately 24 months 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.
Changes in QTcF (ΔQTcF) From Baseline Baseline up to approximately 24 months To assess the effect of dosage regimen and exposure \[active ADC and unconjugated tubulysin\] of BMS-986183 as monotherapy on the QT interval.
Incidence of Positive Anti-drug Antibody (ADA) First dose up to approximately 24 months 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.
Trial Locations
- Locations (1)
Local Institution
🇨🇳Taipei, Taiwan