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Brivanib

Phase 3

Hepato Cellular Carcinoma (HCC) | Small molecule | Oncology |Bristol-Myers Squibb Company|Last Updated: Dec 1, 2023

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindACTIVE_CONTROLLEDDMC
Total Trials1
Total Enrollment1,714

FDA Designations

No designations recorded

Clinical trial landscape

Brivanib · 13 trials · 15 indications

Phase 3 3Phase 2 2Phase 1 8
NCT00908752Phase III Trans-Arterial Chemo-Embolization (TACE) Adjuvant HCCHepatocellular Carcinoma
COMPLETED734 Analytics
NCT00858871First Line Hepato Cellular Carcinoma (HCC)Hepato Cellular Carcinoma (HCC)
COMPLETED1,714 Analytics
NCT00825955Comparison of Brivanib and Best Supportive Care to Placebo for Treatment of Liver Cancer for Those Subjects Who Have Failed Sorafenib TreatmentLiver Cancer
COMPLETED587 Analytics
PHASE3COMPLETED
Phase III Trans-Arterial Chemo-Embolization (TACE) Adjuvant HCC
Hepatocellular CarcinomaUnlock trial analytics
PHASE3COMPLETED
First Line Hepato Cellular Carcinoma (HCC)
Hepato Cellular Carcinoma (HCC)Unlock trial analytics
PHASE3COMPLETED
Comparison of Brivanib and Best Supportive Care to Placebo for Treatment of Liver Cancer for Those Subjects Who Have Failed Sorafenib Treatment
Liver CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

To compare the Overall Survival (OS) of HCC patients who receive brivanib as adjuvant treatments to TACE therapy, with the OS of HCC patients who receive matched placebo with TACE therapy
Survival will be assessed continuously
To compare the overall survival of brivanib versus sorafenib in subjects with advanced HCC who have not received prior systemic treatment
Survival will be assessed continuously
To compare overall survival of subjects with advanced HCC who have progressed on/after or are intolerant to Sorafenib and receive Brivanib plus best supportive care (BSC) to those receiving placebo plus BSC
computerized tomography (CT)/ magnetic resonance imaging (MRI) every six weeks until progression or death
Radiographic imaging and clinical evaluation will be used for tumor assessment
every 6 weeks
Progression Free Survival (PFS) Rate at 6 Months Per Independent Response Review Committee (IRRC) in Cohort A
From first dose up to approximately 6 months after first dose

The percent of participants who have not progressed or died prior to 6 months from the date of their first dose. Participants who have neither progressed nor died but had their last tumor assessment prior to 6 months will not be categorized as progression free and will not be included. Tumor response was measured by the IRRC using mWHO criteria. Progression is defined as a 25% or more increase in the sum of all index lesion areas taking as reference the smallest sum recorded at or following baseline.

The Number of Participants Experiencing Adverse Events (AEs)
From first dose up to 30 days post last dose (up to approximately 34 months)

An Adverse Event (AE) is defined as any new untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have to have a causal relationship with this treatment.

Maximum observed plasma concentration (Cmax) of Brivanib
Days 1, 2, 8, 9 and 15
Trough observed plasma concentration (Cmin) of Brivanib
Days 1, 2, 8, 9 and 15
Time of maximum observed plasma concentration (Tmax) of Brivanib
Days 1, 2, 8, 9 and 15
Area under the plasma concentration-time curve from time zero to the end of the dosing interval [AUC(TAU)] of Brivanib
Days 1, 2, 8, 9 and 15
Average steady state concentration calculated as AUC(TAU)/24 (Css_av) of Brivanib
Days 1, 2, 8, 9 and 15
Degree of fluctuation calculated as ((Cmax- Cmin)/Css_av) [Degree of fluctuation] of Brivanib
Days 1, 2, 8, 9 and 15
Terminal half-life (T-HALF) of Brivanib
Days 1, 2, 8, 9 and 15
Accumulation index calculated as the ratio: AUC(TAU) at steady-state (Day 8) divided by AUC(TAU) after the first dose (Day 1) [AI] of Brivanib
Days 1, 2, 8, 9 and 15
Safety-Toxicity, evaluated according to NCI Common Terminology Criteria for Adverse Events v3.0. Assessments based on medical review of adverse events, results of vital signs, ECGs, echocardiography, physical examinations, and clinical laboratory tests
Cycle 4, Day 1
Pharmacokinetics and markers of exploratory coagulation pathways will be conducted during this trial
PK C1D1-C2-D3, biomarker throughout the study
Safety and tolerability of interventions will be collected
throughout the study on Part II
Dose Limiting Toxicity
at the end of the first cycle of the study
Maximum Tolerated Dose
at the end of the first cycle of the study
Absorption
Determined by PK measurement collected on Day 1 at timepoints 0 (predose) 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18 and 24 hour. Continue daily PK collection on Day 2 to Day 10
Distribution
Determined by PK measurement collected on Day 1 at timepoints 0 (predose) 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18 and 24 hour. Continue daily PK collection on Day 2 to Day 10
Metabolism
Determined by PK measurement collected on Day 1 at timepoints 0 (predose) 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18 and 24 hour. Continue daily PK collection on Day 2 to Day 10
Elimination of BMS-582664
Determined by PK measurement collected on Day 1 at timepoints 0 (predose) 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18 and 24 hour. Continue daily PK collection on Day 2 to Day 10
The primary objective of this study is to determine the effect of BMS-582664 on subjects with varying levels of hepatic impairment and guide prescribers with regards to dosing in specialized populations
throughout the study
Safety assessment
throughout the study
dose-limiting toxicity (DLT)
assessed for individual patients from C1D1 to C1D28 during the dose escalation portion of the protocol, until maximum tolerated dose is identified
determination of maximum tolerated dose (MTD)
during dose escalation portion of the protocol. Three to six subjects are treated at a specified dose level. If deemed safe dose escalation continues until the maximum tolerated dose is identified
To determine the effect on pharmacokinetics of BMS-540215, the active metabolite of brivanib alaninate, when administered following a high fat meal versus administration in a fasted state
throughout the study

Secondary Endpoints

To compare the Time-To-Disease Progression (TTDP) of patients receiving brivanib with TACE therapy to that of patients receiving placebo with TACE therapy
Every 8 weeks
To compare the time to extrahepatic spread or vascular invasion in the brivanib and placebo arms
Every 8 weeks
To determine the total number of TACE sessions in the brivanib and placebo arms and to compare the rate of TACE sessions in the brivanib and placebo arms
End of Study
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
BrivanibACTIVE_COMPARATORAdjuvant treatment with TACE Therapy
Brivanib PlaceboPLACEBO_COMPARATORPlacebo adjuvant treatment with TACE Therapy
SorafenibACTIVE_COMPARATOR -
PlaceboPLACEBO_COMPARATOR -
1EXPERIMENTAL -
2PLACEBO_COMPARATOR -
Arm: BrivanibEXPERIMENTAL -
Arm 1EXPERIMENTAL -
Arm 2EXPERIMENTAL -
Arm 3EXPERIMENTALJapanese Population
Arm 1 - Phase 1ACTIVE_COMPARATORCetuximab + Irinotecan + Brivanib OR Cetuximab + Irinotecan + Brivanib Placebo
Arm 2 - Phase 2PLACEBO_COMPARATORCetuximab + Irinotecan + Brivanib OR Cetuximab + Irinotecan + Brivanib Placebo
3EXPERIMENTAL -
4EXPERIMENTAL -
5EXPERIMENTAL -
6EXPERIMENTAL -

Interventions

NameTypeDescription
BrivanibDRUGTablets, Oral, 200 mg, once daily, until disease progression or toxicity
Brivanib PlaceboOTHERTablets, Oral, 0 mg, once daily, until disease progression or toxicity
TACE TherapyPROCEDURETrans-Arterial Chemo-Embolization Therapy
PlaceboDRUGCapsules, Oral, twice Daily, Until disease progression or unacceptable toxicity
SorafenibDRUGCapsules, Oral, 800 mg, twice daily, Until disease progression or unacceptable toxicity
Best Supportive CarePROCEDURETrans-Arterial Chemo-Embolization (TACE) Therapy
brivanib (active)DRUGTablet, Oral, Brivanib 800 mg, once daily, until progression
5-FUDRUGIV solution, IV bolus over 2-4 minutes, 400 mg/m², Every 14 days, Until disease progression/toxicity
LeucovorinDRUGIV solution, IV over 2 hours, 400 mg/m², Every 14 days, Until disease progression/toxicity
IrinotecanDRUGIV solution, IV over 90 minutes, 180 mg/m², Every 14 days, Until disease progression/toxicity
CetuximabDRUGIV solution, IV, QW, 400 mg/m2 X 1, followed by 250mg/m2, until progression
BrivanabDRUGTablets, Oral, 1000 mg, once daily, until disease progression
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites94

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: * Patients with diagnosis of hepatocellular carcinoma * Cirrhotic status of Child-Pugh Class A or B with a score of 7 * ECOG performance status of 0 or 1 * Adequate hematologi...

Countries:United StatesArgentinaAustraliaCanadaChinaFranceHong KongItalyJapanSouth KoreaSpainTaiwanThailandBelgiumBrazilCzechiaGermanyIndiaMexicoPolandPuerto RicoRussiaSouth AfricaSwedenTurkey (Türkiye)United KingdomGreeceNetherlandsMalaysiaPhilippinesSingaporeDenmark
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Frequently asked questions about Brivanib

What is Brivanib used for?

Brivanib is an investigational small molecule being studied for the treatment of solid tumors, hepatocellular carcinoma (HCC), liver cancer, and gastrointestinal cancers. It has been evaluated in clinical trials for these oncology indications, including advanced or metastatic solid tumors and hepatocellular carcinoma.

Who makes Brivanib?

Brivanib is being developed by Bristol-Myers Squibb Company, which trades under the ticker symbol BMY. The company has sponsored clinical trials of Brivanib in patients with various cancers, including hepatocellular carcinoma and solid tumors.

What phase is Brivanib in?

Brivanib is an investigational drug that has completed Phase 1 and Phase 2 clinical trials. It is not approved by the FDA and remains in clinical development. All three completed trials were uncontrolled, meaning they did not include a comparison group.

What clinical trials has Brivanib been in?

Brivanib has been studied in three completed clinical trials. NCT00355238 was a Phase 2 study in hepatocellular carcinoma with 137 patients. NCT00390936 was a Phase 1 study in advanced solid tumors with 13 patients. NCT00437424 was a Phase 1 study in hepatocellular carcinoma with liver dysfunction, enrolling 24 patients.

Is Brivanib the same as BMS-582664?

Yes, Brivanib is also known as BMS-582664. Clinical trial records refer to the drug by both names, such as in the Phase 2 study of BMS-582664 in hepatocellular carcinoma and the Phase 1 study of Brivanib in liver cancer.