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

NCT03695250 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: 1229924NCI-2018-02009UCDCC#276P30CA093373
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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 or second 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.

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

Outcome Measures

Primary Outcomes (2)

• Adverse Events (AE)

  Number of participants with adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0

  Up to 2 years.

• Objective Response Rate (ORR)

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Up to approximately 2 years, 1 month.

Secondary Outcomes (4)

• Disease Control Rate (DCR)

  Up to 2.5 years

• Progression-free Survival (PFS)

  From date of enrollment to time of progression or death, whichever occurs first, assessed up to 2.5 years

• Duration of Response (DOR)

  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 2.5 years

• Overall Survival (OS)

  From date of enrollment to death from any cause, assessed up to 2.5 years

Study Arms (1)

Treatment (BMS-986205 and nivolumab)

EXPERIMENTAL

Patients 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.

Drug: IDO1 Inhibitor BMS-986205; Biological: Nivolumab

Interventions

IDO1 Inhibitor BMS-986205 DRUG

Given PO

Also known as: BMS 986205, BMS-986205, BMS986205, IDO-1 Inhibitor BMS-986205, Indoleamine-pyrrole 2,3-Dioxygenase Inhibitor BMS-986205, ONO-7701

Treatment (BMS-986205 and nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (BMS-986205 and nivolumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Received more than 1 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
• Active pneumonitis or history of interstitial lung disease (ILD) / pneumonitis requiring steroids
• 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, per investigator descretion
• Participants with a history of G6PD deficiency or other congenital or autoimmune hemolytic disorders. All participants will be screened for G6PD deficiency prior to enrollment 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

Sponsors & Collaborators

• Edward Kim: lead
• Bristol-Myers Squibb: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

linrodostat; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Analyst
• Organization: University of California, Davis

nlogihara@ucdavis.edu

916-734-8053

Study Officials

• Edward Kim

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 2, 2018
• First Posted: October 4, 2018
• Study Start: October 16, 2018
• Primary Completion: November 24, 2020
• Study Completion: March 12, 2021
• Last Updated: August 22, 2023
• Results First Posted: August 22, 2023

Record last verified: 2023-08

Locations

US (1)