Overview

The primary objective of the trial is the safety and tolerability of administering a vaccine targeting the DNAJB1-PRKACA fusion kinase, in combination with nivolumab and ipilimumab in patients with unresectable or metastatic FLC and to assess the T-cell response.

Eligibility

Inclusion Criteria:

• Must have histologically confirmed FLC (fibrolamellar hepatocellular cancer) that is metastatic or unresectable.
• Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-sequencing in the archival tissue.
• Age 12 years. Note: Subjects age 12 years but <18 are eligible to enroll only after 6 adult patients have enrolled on the study.
• Patients < 18 years old must have a body weight 40 kg.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.
• Patients must have measurable disease per RECIST 1.1.
• Patients 18 years old must have an accessible non-bone tumor lesion from which serial core biopsy specimens can be obtained.
• Must be willing to provide tissue and blood samples for mandatory translational research.
• Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.
• Men must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

• Have had chemotherapy or other systemic therapy or radiotherapy, as follows:
• Have had chemotherapy, biological cancer therapy, or radiation 14 days prior to the first dose of study drug.
• Have had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary stent placement.
• Have received other approved or investigational agents or device within 28 days of the first dose of study drug.
• Have not recovered from acute adverse events to grade 1 or baseline due to agents administered
• Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.).
• Have received any non-oncology live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment
• Known sensitivity to or history of allergic reactions to investigational drug (s).
• Hypersensitivity reaction to any monoclonal antibody.
• Has active autoimmune disease that has required systemic treatment in the past 2 years, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
• Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoeitic stem cell transplant will be excluded.
• Has a diagnosis of immunodeficiency.
• Systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 7 days of study drug administration.
• Symptomatic interstitial lung disease.
• Has a pulse oximetry of <92% on room air or is on supplemental home oxygen.
• Active or untreated brain metastases or leptomeningeal metastases.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
• Are pregnant or breastfeeding.
• Infection with HIV or hepatitis B or C.
• Have had evidence of active or acute diverticulitis, intra-abdominal abscess, or GI obstruction.
• Unwilling or unable to follow the study schedule for any reason.
• Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
• Any illicit drugs or other substance abuse.
• Clinically meaningful ascites.