Clinical Trials /

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

NCT04248569

Description:

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.

Related Conditions:
  • Fibrolamellar Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: J19140
  • SECONDARY ID: IRB00222681
  • NCT ID: NCT04248569

Conditions

  • Fibrolamellar Hepatocellular Carcinoma (FLC)

Interventions

DrugSynonymsArms
DNAJB1-PRKACA peptide vaccineHiltonol® (Poly-ICLC)DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab
NivolumabOPDIVODNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab
IpilimumabYERVOY®DNAJB1-PRKACA peptide vaccine, Nivolumab, and Ipilimumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
DNAJB1-PRKACA peptide vaccine, Nivolumab, and IpilimumabExperimental
  • DNAJB1-PRKACA peptide vaccine
  • Nivolumab
  • Ipilimumab

Eligibility Criteria

        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.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants experiencing study drug-related toxicities
Time Frame:4 years
Safety Issue:
Description:Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:4 years
Safety Issue:
Description: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.
Measure:iRECIST Objective response rate (iRORR)
Time Frame:4 years
Safety Issue:
Description:iRORR 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 (iRECIST 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.
Measure:Duration of response (DoR)
Time Frame:4 years
Safety Issue:
Description: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.
Measure:Disease control rate (DCR)
Time Frame:4 years
Safety Issue:
Description: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.
Measure:Progression-free survival (PFS)
Time Frame:4 years
Safety Issue:
Description:PFS is defined as the number of patients with disease progression (progressive disease [PD] 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.
Measure:Immune progression-free survival (irPFS)
Time Frame:4 years
Safety Issue:
Description:irPFS rate is defined as the number of patients with disease progression (PD or death due to any cause. Per immune-related response (irRC) criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in tumor burden compared with baseline, Progressive Disease (PD) is >20% increase in tumor burden compared with nadir, Stable Disease (SD) is <30% decrease in tumor burden compared with baseline or <20% increase in tumor burden compared to nadir. Estimation based on the Kaplan-Meier curve.
Measure:Overall survival (OS)
Time Frame:4 years
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • DNAJB1-PRKACA Peptide Vaccine
  • Nivolumab
  • Ipilimumab
  • Anti-PD-1 (receptor blocking antibody)
  • Anti-CTLA-4 (receptor blocking antibody)
  • Neoantigen Vaccines
  • Cancer Vaccines
  • Immunotherapy
  • Fibrolamellar Hepatocellular Cancer (FLC)

Last Updated

January 28, 2020