Feasibility and Efficacy of Perioperative Nivolumab With or Without Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC)

NCT ID: NCT04658147

Last Updated: 2025-12-18

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-28
• Study Completion Date: 2030-06-01

Brief Summary

The purpose of this study is to determine the safety and tolerability of neoadjuvant/adjuvant Nivolumab or Nivolumab plus Relatlimab in patients with HCC.

Conditions

Hepatocellular Carcinoma

Keywords

Relatlimab; Nivolumab; Immunotherapy; Anti PD-1; Anti - LAG-3; Resectable hepatocellular Cancer; Potentially resectable hepatocellular Cancer; Hepatocellular Cancer (HCC)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A - Nivolumab

Participants receive Nivolumab only.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Nivolumab 480mg will be administered as a 30 minute IV infusion (-/+15min) at cycle 1 day 1 and at cycle 2 day 1 (28 days) then every month for up to 12 months. Intravenous administration of Nivolumab (480 mg) will occur on Cycle 1 and 2 of the study then every 28 days up to a year. Nivolumab will be administered on Day 1 of each cycle for 10 doses/ months (whichever occurs first) for adjuvant.

Arm B - Nivolumab and Relatlimab

Participants receive Nivolumab and Relatlimab.

Group Type: EXPERIMENTAL

Nivolumab

Intervention Type: DRUG

Nivolumab 480mg will be administered as a 30 minute IV infusion (-/+15min) at cycle 1 day 1 and at cycle 2 day 1 (28 days) then every month for up to 12 months. Intravenous administration of Nivolumab (480 mg) will occur on Cycle 1 and 2 of the study then every 28 days up to a year. Nivolumab will be administered on Day 1 of each cycle for 10 doses/ months (whichever occurs first) for adjuvant.

Relatlimab

Intervention Type: DRUG

Patients will receive 480 mg Relatlimab intravenously (-/+15min) on cycle 1 day 1 and at cycle 2 day 1 (every 28 days) for up to 1 year co-administered with Nivolumab.

Interventions

Nivolumab

Nivolumab 480mg will be administered as a 30 minute IV infusion (-/+15min) at cycle 1 day 1 and at cycle 2 day 1 (28 days) then every month for up to 12 months. Intravenous administration of Nivolumab (480 mg) will occur on Cycle 1 and 2 of the study then every 28 days up to a year. Nivolumab will be administered on Day 1 of each cycle for 10 doses/ months (whichever occurs first) for adjuvant.

Intervention Type: DRUG

Relatlimab

Patients will receive 480 mg Relatlimab intravenously (-/+15min) on cycle 1 day 1 and at cycle 2 day 1 (every 28 days) for up to 1 year co-administered with Nivolumab.

Intervention Type: DRUG

Other Intervention Names

OPDIVO™; BMS 936558; MDX1106; ONO-4538; BMS-986016; BMS-986016-01; Anti-LAG-3

Eligibility Criteria

Inclusion Criteria

• Technically resectable HCC as defined by:

• HCC may be diagnosed pathologically, or noninvasively by the American Association for the Study of Liver Diseases (AASLD) criteria or the Organ Procurement and Transplant Network (OPTN) Obligatory Diagnostic Criteria for Hepatocellular Carcinoma (HCC).

No extrahepatic spread, no nodal disease, and no bilateral left and right branch portal vein involvement.

• Measurable disease per RECIST 1.1 as determined by the investigator.
• Age ≥ 18 years old on the day of consent.
• ECOG performance status ≤1 or Karnofsky ≥80.
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.
• Patients must have adequate liver remnant and function.
• Antiviral therapy per local standard of care for hepatitis B.
• LVEF assessment with documented LVEF ≥ 50% by either TTE or MUGA (TTE preferred) within 6 months from first study drug administration.
• Woman of child-bearing potential must have a negative pregnancy test.
• Must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria

• Fibrolamellar carcinoma or mixed HCC.
• Receiving, or previously received, any systemic chemotherapy, or investigational agent for HCC.
• Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, or anti-Lag-3 antibodies.
• Has a known additional malignancy that is expected to require active treatment within two years, or is likely to be life-limiting in the opinion of the treating investigator. Superficial bladder cancer, non-melanoma skin cancers, or low grade prostate cancer not requiring therapy would not exclude participation in this trial.
• History of HIV infection.
• Active co-infection with HBV and HDV.
• Has a diagnosis of immunodeficiency, or is receiving systemic steroid therapy.
• Prior tissue or organ allograft or allogeneic bone marrow transplantation.
• History of any autoimmune disease requiring systemic treatment within the past 2 years.
• Systemic or topical corticosteroids at immunosuppressive doses (> 10 mg/day of prednisone or equivalent).
• Confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
• Uncontrolled intercurrent illness.•
• Uncontrolled or significant cardiovascular disease.
• Significant heart disease.
• Moderate or severe ascites.
• Known or suspected hypersensitivity to study treatment.
• Are pregnant or breastfeeding.
• WOCBP and men with female partners (WOCBP) who are not willing to use contraception.
• Unable to have blood drawn.
• Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
• Any illicit drugs or other substance abuse.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Yarchoan, MD

Role: PRINCIPAL_INVESTIGATOR

SKCCC Johns Hopkins Medical Institution

Locations

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

The Ohio State University, Wexner Medical Center

Columbus, Ohio, United States

Countries

United States

Other Identifiers

IRB00246739

Identifier Type: OTHER

Identifier Source: secondary_id

J20121

Identifier Type: -

Identifier Source: org_study_id