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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03695250
Recruitment Status : Recruiting
First Posted : October 4, 2018
Last Update Posted : February 25, 2020
Sponsor:
Collaborators:
Bristol-Myers Squibb
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Edward Kim, University of California, Davis

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.

Condition or disease Intervention/treatment Phase
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 Drug: IDO1 Inhibitor BMS-986205 Biological: Nivolumab Phase 1 Phase 2

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 or second 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 or second 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of BMS-986205 and Nivolumab as First or Second Line Therapy in Hepatocellular Carcinoma
Actual Study Start Date : October 16, 2018
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : June 1, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

Arm Intervention/treatment
Experimental: Treatment (BMS-986205 and nivolumab)
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
Given PO
Other Names:
  • BMS 986205
  • BMS-986205
  • BMS986205
  • IDO-1 Inhibitor BMS-986205
  • Indoleamine-pyrrole 2,3-Dioxygenase Inhibitor BMS-986205
  • ONO-7701

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo




Primary Outcome Measures :
  1. Incidence of adverse events (AE) [ Time Frame: Up to 100 days ]
    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.

  2. Objective response rate (ORR) [ Time Frame: Up to 3 years ]
    ORR is defined as the percentage of patients that achieve partial response (PR) or complete response (CR). The ORR will be estimated as the proportion of participants who experience an objective response, along with its exact 95% confidence interval.


Secondary Outcome Measures :
  1. Disease control rate (DCR) [ Time Frame: Up to 3 years ]
    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.

  2. Progression-free survival (PFS) [ Time Frame: From date of enrollment to time of progression or death, whichever occurs first, assessed up to 3 years ]
    PFS will be analyzed using Kaplan-Meier methods; medians and 95% confidence intervals will be computed.

  3. 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 ]
    DOR will be analyzed using Kaplan-Meier methods; medians and 95% confidence intervals will be computed.

  4. Overall survival (OS) [ Time Frame: From date of enrollment to death from any cause, assessed up to 3 years ]
    OS will be analyzed using Kaplan-Meier methods; medians and 95% confidence intervals will be computed.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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
  • 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 enrollment
  • Prior history of serotonin syndrome
  • Prior treatment with BMS-986205 or any other IDO1 inhibitors.
  • Women who are breastfeeding
  • History or presence of hypersensitivity or idiosyncratic reaction to methylene blue
  • History of allergy or hypersensitivity to any study treatment components, specifically to that of BMS-986205
  • Participants who have had major surgery requiring general anesthesia or significant trauma who have not recovered per physician determination for at least 14 days prior to enrollment
  • Participants who have had major surgery requiring general anesthesia or significant trauma who have not recovered per physician determination for at least 14 days prior to enrollment
  • Participants with uncontrolled adrenal insufficiency

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03695250


Locations
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United States, California
University of California Davis Comprehensive Cancer Center Recruiting
Sacramento, California, United States, 95817
Contact: Edward J. Kim    916-734-3771    jhkim@ucdavis.edu   
Principal Investigator: Edward J. Kim         
Sponsors and Collaborators
Edward Kim
Bristol-Myers Squibb
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Edward Kim University of California, Davis
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Responsible Party: Edward Kim, Principal Investigator, University of California, Davis
ClinicalTrials.gov Identifier: NCT03695250    
Other Study ID Numbers: 1229924
NCI-2018-02009 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
UCDCC#276 ( Other Identifier: University of California Davis Comprehensive Cancer Center )
P30CA093373 ( U.S. NIH Grant/Contract )
First Posted: October 4, 2018    Key Record Dates
Last Update Posted: February 25, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents