Using Nivolumab with or without Relatlimab for Treating Resectable Liver Cancer

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

This study is testing if the immunotherapy drug Nivolumab, alone or with Relatlimab, can safely help people with liver cancer before and after surgery.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Academic / other)
• Drugs / interventions: chemotherapy, prednisone, Nivolumab, Relatlimab
• Locations: 2 sites (Baltimore, Maryland and 1 other locations)
• Trial ID: NCT04658147 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of administering Nivolumab, an immunotherapy drug, either alone or in combination with Relatlimab, to patients with potentially resectable hepatocellular carcinoma (HCC). The approach involves neoadjuvant and adjuvant treatment phases to assess how well these therapies can be tolerated and their impact on tumor response before and after surgery. Patients will be closely monitored for safety and efficacy outcomes throughout the treatment process.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with technically resectable HCC and no extrahepatic spread or nodal disease.

Not a fit: Patients with advanced HCC that cannot be surgically removed or those with significant comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve surgical outcomes and overall survival rates for patients with hepatocellular carcinoma.

How similar studies have performed: Previous studies have shown promising results with immunotherapy approaches in liver cancer, suggesting potential for success in this novel combination.

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.

Where this trial is running

Baltimore, Maryland and 1 other locations

• Sidney Kimmel Comprehensive Cancer Center — Baltimore, Maryland, United States (Recruiting)
• The Ohio State University, Wexner Medical Center — Columbus, Ohio, United States (Recruiting)

Study contacts

• Principal investigator: Mark Yarchoan, MD — SKCCC Johns Hopkins Medical Institution
• Study coordinator: Colleen Apostal, RN

Conditions Hepatocellular Carcinoma; Relatlimab; Nivolumab; Immunotherapy; Anti PD-1; Anti - LAG-3; Resectable hepatocellular Cancer; Potentially resectable hepatocellular Cancer