Clinical trial NCT04658147: Feasibility and Efficacy of Perioperative Nivolumab With or Without Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC)
Official title: Feasibility and Efficacy of Perioperative Nivolumab With or Without Relatlimab for Patients With Potentially Resectable Hepatocellular Carcinoma (HCC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Keywords: Relatlimab
Nivolumab
Immunotherapy
Anti PD-1
Anti - LAG-3
Resectable hepatocellular Cancer
Potentially resectable hepatocellular Cancer
Hepatocellular Cancer (HCC)
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2020-12-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of patients who complete pre-op treatment and proceed to surgery
timeFrame: 4 years
Secondary outcomes:
measure: Number of participants experiencing study drug-related toxicities
timeFrame: 4 years
measure: Percentage of participants who obtain R0 resection
timeFrame: 8 weeks
measure: Percentage of evaluable patients who obtain a pathologic complete response (pCR) or major pathologic response (MPR)
timeFrame: 8 weeks
measure: Objective response rate (ORR) at 8 weeks
timeFrame: 8 weeks
measure: Overall survival (OS) at 12 months
timeFrame: 12 months
measure: Overall survival (OS) at 18 months
timeFrame: 18 months
measure: Overall survival (OS) at 3 years
timeFrame: 3 years
measure: Overall survival (OS) at 5 years
timeFrame: 5 years
measure: Disease free survival (DFS) at 12 months
timeFrame: 12 months
measure: Disease free survival (DFS) at 18 months
timeFrame: 18 months
measure: Disease free survival (DFS) at 3 years
timeFrame: 3 years
measure: Disease free survival (DFS) at 5 years
timeFrame: 5 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Columbus
country: United States
facility: The Ohio State University, Wexner Medical Center
state: Ohio
Study officials:
affiliation: SKCCC Johns Hopkins Medical Institution
name: Mark Yarchoan, MD
role: PRINCIPAL_INVESTIGATOR
References: