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.
- Must have histologically confirmed FLC (fibrolamellar hepatocellular cancer) that is
metastatic or unresectable.
- Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-sequencing, DNA
sequencing, or in situ hybridization 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
- 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.
- 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
- 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
- Unwilling or unable to follow the study schedule for any reason.
- Any other sound medical, psychiatric, and/or social reason as determined by the
- Any illicit drugs or other substance abuse.
- Clinically meaningful ascites.