Clinical Trials /

BMS-986205 and Nivolumab as First Line Therapy in Treating Patients With Liver Cancer

NCT03695250

Description:

This phase I/II trial studies the side effects and best dose of IDO1 inhibitor BMS-986205 (BMS-986205) when given together with nivolumab and how well it works as first line therapy in treating patients with liver cancer. BMS-986205 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving BMS-986205 and nivolumab may work better in treating patients with liver cancer.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: BMS-986205 and Nivolumab as First Line Therapy in Treating Patients With Liver Cancer
  • Official Title: Phase I/II Trial of BMS-986205 and Nivolumab as First Line Therapy in Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 1229924
  • SECONDARY ID: NCI-2018-02009
  • SECONDARY ID: UCDCC#276
  • SECONDARY ID: P30CA093373
  • NCT ID: NCT03695250

Conditions

  • Metastatic Hepatocellular Carcinoma
  • Stage III Hepatocellular Carcinoma AJCC v8
  • Stage IIIA Hepatocellular Carcinoma AJCC v8
  • Stage IIIB Hepatocellular Carcinoma AJCC v8
  • Stage IV Hepatocellular Carcinoma AJCC v8
  • Stage IVA Hepatocellular Carcinoma AJCC v8
  • Stage IVB Hepatocellular Carcinoma AJCC v8
  • Unresectable Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
IDO1 Inhibitor BMS-986205BMS 986205, BMS-986205, BMS986205, IDO-1 Inhibitor BMS-986205, Indoleamine-pyrrole 2,3-Dioxygenase Inhibitor BMS-986205, ONO-7701Treatment (BMS-986205 and nivolumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (BMS-986205 and nivolumab)

Purpose

This phase I/II trial studies the side effects and best dose of IDO1 inhibitor BMS-986205 (BMS-986205) when given together with nivolumab and how well it works as first line therapy in treating patients with liver cancer. BMS-986205 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving BMS-986205 and nivolumab may work better in treating patients with liver cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To obtain the safety and tolerability of BMS-986205 in combination with nivolumab in
      unresectable / metastatic hepatocellular carcinoma (HCC) in the first line setting using
      Common Terminology Criteria for Adverse Events (CTCAE) version (V)5.0 criteria.

      II. To determine efficacy as defined by objective response rate (ORR) of BMS-986205 in
      combination with nivolumab in unresectable / metastatic HCC in the first line setting using
      Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1).

      SECONDARY OBJECTIVES:

      I. To determine disease control rate (DCR), duration of response (DOR), progression free
      survival (PFS), and overall survival (OS) by RECIST 1.1 and ORR using immune RECIST (iRECIST)
      of BMS-986205 in combination with nivolumab in unresectable HCC. (Phase II) II. To further
      evaluate safety of BMS-986205 in combination with nivolumab in unresectable HCC. (Phase II)

      OUTLINE: This is a phase I, dose-escalation study of IDO1 inhibitor BMS-986205 followed by a
      phase II study.

      Patients receive IDO1 inhibitor BMS-986205 orally (PO) once daily (QD) on days 1-14 and
      nivolumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 14 days in the
      absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 100 days, and then every 3
      months thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (BMS-986205 and nivolumab)ExperimentalPatients receive IDO1 inhibitor BMS-986205 PO QD on days 1-14 and nivolumab IV over 30 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
  • IDO1 Inhibitor BMS-986205
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Willing and able to provide written informed consent for the trial

          -  Life expectancy > 12 weeks

          -  Histologically or imaging confirmed hepatocellular carcinoma (mixed
             hepatocellular/cholangiocarcinoma or fibrolamellar subtypes are excluded)

          -  Have disease that is not amenable for curative treatment approach

          -  Have measurable disease based on RECIST v1.1

          -  >= 1 liver lesions accessible for core biopsy that was either not previously treated
             by liver-directed therapy or progressed following liver-directed therapy

          -  Child-Pugh score of A

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Absolute neutrophil count (ANC) >= 1000 cell/mm^3

          -  Platelet count >= 50,000/mm^3

          -  Hemoglobin (Hgb) >= 8 g/dL

          -  Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT),
             alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =< 5 x upper
             limit of normal (ULN)

          -  Total bilirubin =< 2 ULN

          -  Creatinine =< 2 x ULN

          -  Subjects with active hepatitis B virus (hep B) are allowed if antiviral therapy for
             hepatitis B has been given for > 8 weeks and viral load is < 100 IU/ml prior to first
             dose of trial treatment. Subjects with untreated hepatitis C virus (HCV) are allowed

          -  Willingness to undergo mandatory pre-treatment biopsy (unless there is adequate
             archival tumor specimen available) and mandatory on-treatment biopsy

          -  Female subject of child-bearing potential must have a negative urine pregnancy =< 24
             hour (hr) prior to planned treatment initiation. Women with childbearing potential and
             males must be willing to use adequate birth control on trial and until 5 months for
             women or 7 months for men after the last of study therapy

          -  Ability to adhere to the study visit schedule and other protocol requirements

          -  Participants must be able to swallow pills intact

        Exclusion Criteria:

          -  Received prior systemic HCC-related therapy or currently receiving HCC-related
             systemic treatment or participating in a clinical trial and receiving study therapy

          -  Known history of positive test for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS)

          -  Known diagnosis of immunodeficiency or active autoimmune disease or requiring systemic
             steroid equivalent of prednisone >= 10 mg/day or any immunosuppressive therapies =< 7
             days of before the first dose of the study

          -  Active bacterial, viral (except hepatitis B and C), or fungal infection(s) requiring
             systemic therapy, defined as ongoing signs/symptoms related to the infection without
             improvement despite appropriate antibiotics, anti-viral therapy, anti-fungal therapy,
             and/or other treatment

          -  Known history of pneumonitis (non-infectious) or evidence of interstitial lung disease

          -  Clinically significant ascites

          -  Hepatic encephalopathy

          -  Any significant medical condition including additional malignancies, laboratory
             abnormalities, or psychiatric illness that would prevent the subject from
             participating and adhering to study related procedures

          -  Live attenuated vaccine =< 30 days before the first dose of study treatment. Examples
             of live vaccines include, but are not limited to, the following: measles, mumps,
             rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and
             typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus
             vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are
             live attenuated vaccines and are not allowed

          -  Use of strong inhibitor / inducer of CYP3A4 or CYP1A2

          -  Known history of surgery or medical condition that may affect drug absorption

          -  Participants with a history of G6PD deficiency or other congenital or autoimmune
             hemolytic disorders. All participants will be screened for G6PD deficiency prior to
             randomization using quantitative or qualitative G6PD assay results to suggest
             underlying G6PD deficiency

          -  Participants with a personal or family (i.e., in a first-degree relative) history or
             presence of cytochrome b5 reductase deficiency (previously called methemoglobin
             reductase deficiency) or other diseases that puts them at risk of methemoglobinemia.
             All participants will be screened for methemoglobin levels prior to enrollment using
             blood methemoglobin > ULN, assessed in an arterial or venous blood sample or by co
             oximetry

          -  Subjects with screening corrected QT (QTc) interval > 480 ms

          -  Liver directed therapy =< 4 weeks before the first dose of study

          -  History of esophageal or gastric variceal bleeding within 3 months of study enrollment

          -  Treatment with botanical preparations (e.g., herbal supplements or traditional Chinese
             medicines) intended for general health support or to treat the disease under study
             within 2 weeks prior to randomization

          -  Prior history of serotonin syndrome
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AE)
Time Frame:Up to 100 days
Safety Issue:
Description:Safety profile will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (V)5.0 criteria. Dose-limiting toxicities (DLTs), adverse events, serious adverse events, and clinical laboratory values outside normal limits will be listed for each patient and summarized by body system and dose level in frequency tables.

Secondary Outcome Measures

Measure:Disease control rate (DCR)
Time Frame:Up to 3 years
Safety Issue:
Description:DCR is defined as the percentage of patients that achieve an objective tumor response or have stable disease to therapy. The DCR will be estimated as the proportion of participants who experience an objective response, along with its exact 95% confidence interval.
Measure:Progression-free survival (PFS)
Time Frame:From date of enrollment to time of progression or death, whichever occurs first, assessed up to 3 years
Safety Issue:
Description:PFS will be analyzed using Kaplan-Meier methods; medians and 95% confidence intervals will be computed.
Measure:Duration of response (DOR)
Time Frame:From the time measurement criteria are met for CR or PR (whichever status is recorded first) until the first date that recurrence or progressive disease (PD) is objectively documented, assessed up to 3 years
Safety Issue:
Description:DOR will be analyzed using Kaplan-Meier methods; medians and 95% confidence intervals will be computed.
Measure:Overall survival (OS)
Time Frame:From date of enrollment to death from any cause, assessed up to 3 years
Safety Issue:
Description:OS will be analyzed using Kaplan-Meier methods; medians and 95% confidence intervals will be computed.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Edward Kim

Last Updated