RECRUITING

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

Conditions

Fibrolamellar Hepatocellular Carcinoma (FLC)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)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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 with non-FLC solid tumors and to assess the T-cell response.

Official Title

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

Quick Facts

Study Start:2020-04-20

Study Completion:2027-03-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04248569

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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. * • 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. * 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.	* 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). * 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

Exclusion Criteria

* 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.
* • 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.
* 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.

* 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).
* 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.

Contacts and Locations

Study Contact

Colleen Apostol, RN

CONTACT

410-614-3644

GIClinicalTrials@jhmi.edu

Marina Baretti, MD

CONTACT

410-614-1058

mbarett1@jhu.edu

Principal Investigator

Mark Yarchoan, MD

PRINCIPAL_INVESTIGATOR

Johns Hopkins Medical Institution

Study Locations (Sites)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231

United States

Collaborators and Investigators

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Mark Yarchoan, MD, PRINCIPAL_INVESTIGATOR, Johns Hopkins Medical Institution

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-04-20

Study Completion Date2027-03-01

Study Record Updates

Study Start Date2020-04-20

Study Completion Date2027-03-01

Terms related to this study

Keywords Provided by Researchers

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)

Additional Relevant MeSH Terms

Fibrolamellar Hepatocellular Carcinoma (FLC)