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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04658147
• Other study ID #: J20121
• Secondary ID: IRB00246739
• Status: Recruiting
• Phase: Phase 1
• Start date: May 28, 2021
• Est. completion date: June 1, 2026

Study information

• Verified date: January 2024
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: Colleen Apostal, RN
• Phone: 410-614-3644
• Email: GIClinicalTrials[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 1, 2026
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	The Ohio State University, Wexner Medical Center	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients who complete pre-op treatment and proceed to surgery		4 years
Secondary	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
Secondary	Percentage of participants who obtain R0 resection		8 weeks
Secondary	Percentage of evaluable patients who obtain a pathologic complete response (pCR) or major pathologic response (MPR)		8 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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