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

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

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Nivolumab; Drug: Relatlimab

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Joann Santmyer, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu
• Study Contact Backup: Name: Colleen Apostal, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • Sidney Kimmel Comprehensive Cancer Center
      • Principal Investigator: Mark Yarchoan, MD
      • Contact: Bradley Wilt, RN; Phone Number: 410-614-1816; Email: bwilt1@jhmi.edu
      • Contact: Trish Brothers, RN; Phone Number: 410-614-3644; Email: GIClinicaltrials@jhmi.edu
  • Ohio
    • Columbus, Ohio, United States, 43210-1002
      • Recruiting
      • The Ohio State University, Wexner Medical Center
      • Principal Investigator: Aslam Ejaz, MD
      • Contact: Barbara Kleiber, MACPR, BSN, RN, OCN, CCRC; Phone Number: 614-293-1815; Email: Barbara.kleiber@osumc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A - Nivolumab; Participants receive Nivolumab only.	Drug: 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.; Other Names: ONO-4538; MDX1106; OPDIVO™; BMS 936558
Experimental: Arm B - Nivolumab and Relatlimab; Participants receive Nivolumab and Relatlimab.	Drug: 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.; Other Names: ONO-4538; MDX1106; OPDIVO™; BMS 936558; 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.; Other Names: BMS-986016; Anti-LAG-3; BMS-986016-01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients who complete pre-op treatment and proceed to surgery	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants experiencing study drug-related toxicities	Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0.	4 years
Percentage of participants who obtain R0 resection		8 weeks
Percentage of evaluable patients who obtain a pathologic complete response (pCR) or major pathologic response (MPR)		8 weeks
Objective response rate (ORR) at 8 weeks	ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.	8 weeks
Overall survival (OS) at 12 months	OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.	12 months
Overall survival (OS) at 18 months	OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.	18 months
Overall survival (OS) at 3 years	OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.	3 years
Overall survival (OS) at 5 years	OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.	5 years
Disease free survival (DFS) at 12 months	Number of months from the date of first treatment until disease recurrence at 12 months. Estimation based on the Kaplan-Meier curve.	12 months
Disease free survival (DFS) at 18 months	Number of months from the date of first treatment until disease recurrence at 18 months. Estimation based on the Kaplan-Meier curve.	18 months
Disease free survival (DFS) at 3 years	Number of months from the date of first treatment until disease recurrence at 3 years. Estimation based on the Kaplan-Meier curve.	3 years
Disease free survival (DFS) at 5 years	Number of months from the date of first treatment until disease recurrence at 5 years. Estimation based on the Kaplan-Meier curve.	5 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Mark Yarchoan, MD, SKCCC Johns Hopkins Medical Institution

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (Actual): December 8, 2020

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Nivolumab; Immunotherapy; Relatlimab; Anti PD-1; Anti - LAG-3; Resectable hepatocellular Cancer; Potentially resectable hepatocellular Cancer; Hepatocellular Cancer (HCC)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Relatlimab
• Other Study ID Numbers: J20121; IRB00246739 (Other Identifier: Johns Hopkins Medical Internal Review Board)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No