A Phase 1/2 interventional study of BMS-986183 and Nivolumab in Hepatocellular Carcinoma, sponsored by Bristol-Myers Squibb. Terminated at 4 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-01-30.
Sponsored by Bristol-Myers Squibb · Phase 1/2, Interventional, and Treatment
The purpose of this study is to evaluate the safety and tolerability of BMS-986183 in patients with liver cancer.
6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.
This study's enrollment of 25 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.
Browse Carcinoma studies →Bristol-Myers Squibb is the lead sponsor of 1,538 studies on the registry; 116 are open to participants now.
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Inclusion Criteria:
Exclusion Criteria:
Other protocol defined inclusion/exclusion criteria could apply
Biological: BMS-986183
Biological: BMS-986183
Biological: BMS-986183 · Biological: Nivolumab
Biological: BMS-986183 · Biological: Nivolumab
specified dose on specified days
specified dose on specified days
Also known as: BMS-936558, Opdivo
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: First dose up to approximately 24 months
Incidence of Laboratory Test Toxicity Grade Shifting From Baseline
Time frame: First dose up to approximately 24 months
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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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)\]
Time frame: 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).
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: First dose up to approximately 24 months
There were 10 subjects were treated in this study. All 10 subjects were enrolled in BMS-986183 escalation (Part 1)
| Milestone | BMS-986183 3 mg | BMS-986183 9 mg | BMS-986183 18 mg | BMS-986183 36 mg |
|---|---|---|---|---|
| Started | 1 | 2 | 1 | 6 |
| Completed | 0 | 0 | 0 | 0 |
| Not completed | 1 | 2 | 1 | 6 |
| Withdrew: Disease progression | 1 | 2 | 1 | 4 |
| Withdrew: Ae unrelated to study drug | 0 | 0 | 0 | 1 |
| Withdrew: Subject withdrew consent | 0 | 0 | 0 | 1 |
Evaluated by comparing the incidence of Adverse Events (AEs) among subjects using their assigned treatment for at least one day.
No measurements were reported for this outcome.
Evaluated by comparing the incidence of Serious Adverse Events (SAEs) among subjects using their assigned treatment for at least one day.
No measurements were reported for this outcome.
Evaluated by comparing the incidence of Adverse Events leading to discontinuation among subjects using their assigned treatment for at least one day.
No measurements were reported for this outcome.
Evaluated by comparing the incidence of Adverse Events leading to death among subjects using their assigned treatment for at least one day.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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
No measurements were reported for this outcome.
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
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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
No measurements were reported for this outcome.
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
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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)\]
No measurements were reported for this outcome.
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).
No measurements were reported for this outcome.
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
No measurements were reported for this outcome.
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)
No measurements were reported for this outcome.
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
No measurements were reported for this outcome.
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
No measurements were reported for this outcome.
(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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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).
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
To assess the effect of dosage regimen and exposure \[active ADC and unconjugated tubulysin\] of BMS-986183 as monotherapy on the QT interval.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
Collected over First dose up to approximately 24 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| BMS-986183 ESC 3 mg | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| BMS-986183 ESC 9 mg | 2/2 (100%) | 1/2 (50%) | 2/2 (100%) |
| BMS-986183 ESC 18 mg | 0/1 (0%) | 1/1 (100%) | 1/1 (100%) |
| BMS-986183 ESC 36 mg | 5/6 (83.3%) | 2/6 (33.3%) | 5/6 (83.3%) |
| Event | BMS-986183 ESC 3 mg | BMS-986183 ESC 9 mg | BMS-986183 ESC 18 mg | BMS-986183 ESC 36 mg |
|---|---|---|---|---|
| Lung infectionInfections and infestations | 0/1 | 0/2 | 1/1 | 0/6 |
| Upper respiratory tract infectionInfections and infestations | 0/1 | 0/2 | 1/1 | 0/6 |
| GastroenteritisInfections and infestations | 0/1 | 1/2 | 0/1 | 0/6 |
| Oesophageal varices haemorrhageGastrointestinal disorders | 0/1 | 0/2 | 0/1 | 1/6 |
| Hepatic failureHepatobiliary disorders | 0/1 | 0/2 | 0/1 | 1/6 |
| Hepatic cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/1 | 0/2 | 0/1 | 1/6 |
| Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/1 | 0/2 | 0/1 | 1/6 |
| Event | BMS-986183 ESC 3 mg | BMS-986183 ESC 9 mg | BMS-986183 ESC 18 mg | BMS-986183 ESC 36 mg |
|---|---|---|---|---|
| PalpitationsCardiac disorders | 0/1 | 0/2 | 1/1 | 0/6 |
| Abdominal distensionGastrointestinal disorders | 0/1 | 1/2 | 1/1 | 0/6 |
| DiarrhoeaGastrointestinal disorders | 0/1 | 0/2 | 1/1 | 1/6 |
| NauseaGastrointestinal disorders | 0/1 | 0/2 | 1/1 | 1/6 |
| VomitingGastrointestinal disorders | 0/1 | 0/2 | 1/1 | 1/6 |
| FatigueGeneral disorders | 1/1 | 1/2 | 1/1 | 3/6 |
| PainGeneral disorders | 0/1 | 0/2 | 1/1 | 0/6 |
| Upper respiratory tract infectionInfections and infestations | 0/1 | 0/2 | 1/1 | 0/6 |
| Decreased appetiteMetabolism and nutrition disorders | 0/1 | 1/2 | 1/1 | 3/6 |
| HyperkalaemiaMetabolism and nutrition disorders | 0/1 | 2/2 | 0/1 | 0/6 |
All treated paritcipants
| Age, Continuous(Years) | BMS-986183 3 mg | BMS-986183 9 mg | BMS-986183 18 mg | BMS-986183 36 mg | Total |
|---|---|---|---|---|---|
| Mean | 56.0 ± NA | 67.5 ± 4.9 | 57.0 ± NA | 49.5 ± 8.6 | 54.5 ± 10.0 |
| Sex: Female, Male(Participants) | BMS-986183 3 mg | BMS-986183 9 mg | BMS-986183 18 mg | BMS-986183 36 mg | Total |
|---|---|---|---|---|---|
| Female | 0 | 0 | 0 | 1 | 1 |
| Male | 1 | 2 | 1 | 5 | 9 |
| Race/Ethnicity, Customized(Participants) | BMS-986183 3 mg | BMS-986183 9 mg | BMS-986183 18 mg | BMS-986183 36 mg | Total |
|---|---|---|---|---|---|
| White | 0 | 0 | 0 | 1 | 1 |
| Black or African American | 0 | 0 | 0 | 0 | 0 |
| Asian | 1 | 2 | 1 | 5 | 9 |
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