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Fibrolamellar Carcinoma

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Immunologic Factors

1. DNAJB1-PRKACA peptide vaccine: Day 1, 8, 15 of cycle 1 and Day 1 of cycle 2, 3, 4 and 5 (priming phase). Boost vaccinations: every 3 cycles beginning C6D1. For Cohort A-(Initial) only: Patients with FLC cancer with no prior checkpoint inhibitor therapy treatment.
2. DNAJB1-PRKACA peptide vaccine: Day 1, 8, 15 of cycle 1 and on Day 1 of cycle 2, 3 and 4 (priming phase). Boost vaccinations: every 3 cycles beginning C5D1.

   * Cohort A-(Expansion): Patients with FLC cancer with no prior checkpoint inhibitor treatment.
   * Cohort B: Patients with FLC cancer with prior checkpoint inhibitor treatment.
   * Cohort C: Patients with non-FLC cancer (solid tumors) with prior checkpoint inhibitor treatment eligible.
3. Drug: 0.3 mg DNAJB1-PRKACA peptide vaccine + 0.5mg Poly-ICLC

DNAJB1-PRKACA peptide vaccine

1. Cohort A (Initial): Nivolumab 3mg/kg will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycle 2-5 during the priming phase. Boost/maintenance vaccinations will be administered as a flat dose of 480mg every 4 weeks starting on Day 1 of Cycle 6.
2. Cohort A (Expansion), B and C: Nivolumab 3mg/kg will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycle 1-4 during the priming phase. Boost/maintenance vaccinations will be administered as a flat dose of 480mg every 4 weeks starting on Day 1 of Cycle 5.
3. Drug: 3mg/kg and 480mg IV

1. Cohort A (Initial): Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycles 2, 3, 4 and 5 of the study, every 3 weeks of the priming phase.
2. Cohort A (Expansion), B and C: Ipilimumab (1 mg/kg) will be administered as a 30 minute IV infusion (-10/+15min) on Day 1 of Cycles 1, 2, 3 and 4 of the study, every 3 weeks of the priming phase.
3. Drug: 1mg/kg IV

Colleen Apostol, RN

Marina Baretti, MD

Mark Yarchoan, MD

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.

DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma

A Pilot Study of a DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma

Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0

Evaluated by the fold change in interferon-producing DNAJB1-PRKACA-specific CD8 cells after vaccination at 10 weeks compare to pre-vaccination baseline.

Evaluated by the fold change in interferon-producing DNAJB1-PRKACA-specific CD4 T cells after vaccination at 10 weeks compare to pre-vaccination baseline.

ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

Number of weeks from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date of disease progression or death is documented per RECIST 1.1. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions.

DCR is defined as the number of patients achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

PFS is defined as number of months from the date of first treatment until first documented local progression or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.

OS will be measured from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma	NCT04248569	Fibrolamellar H...	DNAJB1-PRKACA p... Nivolumab Ipilimumab	12 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma	NCT04248569	Fibrolamellar H...	DNAJB1-PRKACA p... Nivolumab Ipilimumab	12 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for fibrolamellar hepatocellular cancer (flc)