Inclusion Criteria for Cohort A, B and C:
* Cohort A and B: Must have histologically confirmed FLC (fibrolamellar hepatocellular cancer) that is metastatic or unresectable.
* Cohort C: Patients with histologically proven metastatic or unresectable DNAJB1-PRKACA fusion transcript positive solid tumor malignancies, non-FLC solid tumors.
* Cohort A and B: Age \> 12 years. Note: Subjects age \> 12 years but \<18 are eligible to enroll only after 6 adult patients have enrolled on the study.
* Cohort A and B: Patients \< 18 years old must have a body weight ≥40 kg.
* Cohort C: Patients must be Age ≥ 18 years.
All Cohorts:
* Presence of DNAJB1-PRKACA fusion transcript, assessed by RNA-sequencing, DNA-sequencing, or in situ hybridization in the archival tissue.
* ECOG performance status of ≤2 (Karnofsky ≥60%)
* Patients must have adequate liver, kidney and marrow function defined by study-specified laboratory tests prior to initial study drug.
* Patients must have measurable disease per RECIST 1.1.
* 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 for Cohorts A, B and C:
* Cohort A and C: Patients with a history of prior treatment with checkpoint inhibitors, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4, or anti-LAG-3 antibodies. NOTE: Prior therapy with interferon-alpha is allowed.
* Cohort B: Participants a with history of unacceptable, life-threatening toxicity related to prior immune therapy (eg, anti-CTLA-4 or anti-PD-1/PD-L1 treatment, any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg, hormone replacement after endocrinopathy).
All Cohorts:
* 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.
* 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.
Inclusion Criteria for Re-Enrolling Patients:
* Patients previously treated with the vaccine targeting the DNAJB1-PRKACA fusion kinase in combination with nivolumab and ipilimumab, who, in the opinion of the principal investigator, had clinical or radiological benefits.
* Patients \< 18 years old must have a body weight ≥40 kg.
* ECOG performance status of ≤2 (Karnofsky ≥60%, see Appendix A).
* Patients must have adequate liver, kidney and marrow function defined by study-specified laboratory tests prior to initial study drug.
* Patients must have measurable disease per RECIST 1.1.
* Willingness 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 for Re-Enrolling Patients:
* Participants with a history of prior unacceptable and/or life-threatening toxicities.
* Patients who have had chemotherapy or other systemic therapy or radiotherapy, as follows:
* Patients who have had chemotherapy, biological cancer therapy, or radiation 14 days prior to the first dose of study drug.
* Patients who 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.
* Patients who have received other approved or investigational agents or device within 28 days of the first dose of study drug.
* Patients who have not recovered from acute adverse events to grade ≤1 or baseline due to agents administered, with exception of alopecia or stable neuropathy, unless approved by the IND Sponsor.
* Patients who 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.
* 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.
