Several clinical trials are currently underway that have been specifically designed for fibrolamellar patients. These efforts include trials to test new treatments that specifically target the DNAJB1::PRKACA fusion that drives the disease, or other treatments that have shown promising activity in pre-clinical research. Summaries of each trial can be read below:
Current FLC clinical trials
Study status: Active, recruiting
This phase I clinical trial is now recruiting subjects at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, MD. The study will test the safety and effectiveness the experimental prodrug DRP-104 in combination with an immune checkpoint inhibitor for patients with advanced stage FLC. DRP-104 is an inactive compound that is converted into a broad-acting glutamine antagonist within tumors, while mostly remaining inactivated in other healthy tissues. This study will test the hypothesis that blocking FLC’s glutamine metabolism can directly cause the death of FLC cancer cells, and also enhance a patient’s own anti-cancer immune response. (Click here to learn more about exploiting FLC’s potential metabolic weaknesses.)
While enrollment in this trial is currently open only to FLC patients 18 years old or older, enrollment should soon be open to FLC patients 12 years old and older. For more information about this study, please visit clinicaltrials.gov (NCT06027086) or contact the clinical trials team at Johns Hopkins at GIClinicalTrials@jhmi.edu.
In the video below, Dr. Marina Baretti and Dr. Mark Yarchoan of Johns Hopkins discuss the pre-clinical work that provided the scientific rationale for the effort, as well as the design and enrollment criteria for the study:
Trial contact information:
- Anna Ferguson, RN – afergus1@jhmi.edu
- Marina Baretti, MD – mbarett1@jhu.edu
Study status: Active, recruiting
This phase I clinical trial of an immune therapy for fibrolamellar carcinoma (FLC) is now recruiting subjects at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, MD. The study asks if individuals can mount an effective immune response against FLC by specifically targeting the unique chimeric protein (resulting from a DNAJB1-PRKACA gene fusion) believed to drive the growth of almost all such tumors. Trial subjects will be given an experimental vaccine (the first patient in the trial received this vaccine on April 21, 2020) containing a peptide (small segment of a protein) that corresponds to the junction region linking the two parts of the chimeric protein. They will simultaneously receive two FDA-approved drugs, Opdivo (nivolumab) and Yervoy (ipilimumab), that may enhance the immune response against FLC by overcoming “checkpoint” systems that can limit the immune system’s ability to fight a cancer.
Enrollment in this trial is open to FLC patients 12 years old and older. The study’s principal investigator is Dr. Mark Yarchoan. More detail can be found at: https://www.clinicaltrials.gov/study/NCT04248569.
Dr. Mark Yarchoan, the principal investigator of this trial, discusses the rationale for the FLC fusion peptide vaccine, the accompanying drug regimen and the eligibility criteria for this first-in-human study in the video below:
Trial contact information:
- Anna Ferguson, RN – afergus1@jhmi.edu
- Marina Baretti, MD – mbarett1@jhu.edu
Study status: Active, recruiting
This phase I clinical trial will evaluate the immunogenicity, safety, and first efficacy of a DNAJB1-PRKACA fusion transcript-based peptide vaccine (Fusion-VAC-XS15) delivered in combination with the immune checkpoint inhibitor Atezolizumab (TecentriqTM). The study is expected to enroll 20 patients with fibrolamellar carcinoma or other cancers carrying the DNAJB1-PRKACA fusion transcript. It is being conducted by the network of Centers for Personalized Medicine (ZPM) at the University Hospitals of Freiburg, Heidelberg, Tübingen and Ulm in Baden-Württemberg, Germany. The initial Tübingen site is now open.
These researchers are looking into the viability of using a peptide immunization to give a patient’s immune system the ability to identify and destroy “foreign” FLC cells. The peptide vaccine, made from a fragment of the fusion region of FLC’s DNAJB1-PRKACA fusion protein, is being manufactured at the University Hospital Tübingen.
Enrollment in this trial is open to patients 18 years old and older whose disease has the confirmed presence of the DNAJB1-PRKACA fusion transcript.
Participants will be required to visit the Tübingen study center once prior to beginning treatment. Blood will be drawn at the preliminary examination, and research participation eligibility will be determined. The Fusion-VAC-XS15 peptide vaccine will be administered to research participants at least twice during the course of the investigation. In addition, atezolizumab will be given intravenously as an infusion every four weeks. The course of treatment is set over one year.
Details about the study can be found on the University Hospital Tübingen web site (click here for a summary of the study in English) and at https://clinicaltrials.gov/study/NCT05937295. In addition, this linked article, published in Frontiers in Oncology in March 2024 provides more information about the study protocol.
Dr. Juliane Walz, an investigator for this trial, discusses the goals, rationale, design, and eligibility criteria for this clinical study in the video below:
Trial contact information:
- Juliane Walz, Prof. Dr. – kketi@med.uni-tuebingen.de
Study status: Active, recruiting
This phase I study will assess the safety and efficacy of a peptide vaccine (Fusion-VAC-XS15) against FLC’s driver protein as an “adjuvant” therapy in FLC patients who, after surgery and/or other treatment, are free of cancer as judged by radiological scans. The goal is to significantly delay or entirely prevent the return of the cancer. The vaccine will be given alone, without additional immunotherapy or any other systemic agent.
Recurrence rates of FLC after successful surgery, liver transplantation, or systemic therapy are quite high. A recent case report documented disease recurrence in a fibrolamellar patient nearly two decades after the apparently successful resection of the initial tumor. In this trial, the study team hopes to use a peptide vaccine to activate the immune system against any remaining tumor cells and enable long-term disease-free survival.
Enrollment in this trial will be open to patients whose disease has the confirmed presence of the DNAJB1-PRKACA fusion transcript and who have achieved complete remission (CR) status according to RECIST1.1. Initially all patients must be 18 years old or older. Patients 12 years and older will be eligible to participate after 6 adult patients have been enrolled in the study.
During the trial, the FusionVAC-22 peptide will be administered subcutaneously. A total of two vaccinations are planned for each patient, delivered 4 weeks apart. If an insufficient T cell response is detected after the two-vaccine treatment, a booster vaccination can be applied.
Details about the study can be found on the University Hospital Tübingen web site and at https://clinicaltrials.gov/study/NCT06789198.
In the video below, Dr. Juliane Walz discusses the goals and design for this clinical study, as well as the differences between the two peptide vaccine trials currently underway in Tübingen, Germany:
Trial contact information:
- Juliane Walz, Prof. Dr. – kketi@med.uni-tuebingen.de
Study status: Pending, opening soon
This phase I/II clinical trial will evaluate the safety, side effects, and optimal dosage of DT2216 combined with irinotecan, as well as its effectiveness in treating children, adolescents, and young adults with relapsed (returned after improvement) or refractory (non-responsive to prior treatment) FLC. DT2216 is a targeted protein degrader that inhibits BCL-XL, an anti-apoptotic protein essential for tumor cell survival, potentially stopping tumor growth. Irinotecan, a topoisomerase I inhibitor, disrupts cell division and DNA repair, which may lead to tumor cell death.
The clinical trial is based on research led by Sandy Simon, PhD of Rockefeller University that showed that FLC cells are sensitive to irinotecan, but that sensitivity is inversely correlated with the cells’ expression of BCL-XL.
DT2216 is an investigational drug developed by Dialectic Therapeutics that avoids a complication found with conventional BCL-XL inhibitors – impaired blood clotting caused by a drop in the number of platelets, which are rich in BCL-XL. Dialectic Therapeutics has previously completed a Phase 1 first-in-human study of DT2216 in patients with various cancers. This trial established DT2216’s safety and tolerability, and it confirmed that the drug does not cause thrombocytopenia (low platelet count). The initial trial also established a phase 2 dose for the single agent, and it laid solid groundwork for this study of DT2216 in combination with irinotecan.
The initial Phase 1 portion of this study will be carried out in patients between ages 1 and 21 years with recurrent and/or treatment-refractory solid tumors. This phase will include FLC patients; however, many subjects may have other cancers. Its main goal will be to determine a recommended Phase 2 dose of DT2216, administered in combination with a standard dose of irinotecan. The study also will assess the pharmacokinetics of DT2216 (how the drug is absorbed, distributed, chemically altered, and excreted by the body), and its toxicities. Finally, this component of the study will assess, to the extent possible, the anti-tumor activity of DT2216 in combination with irinotecan in patients with solid tumors, including any patients with FLC. Between 6 and 24 evaluable patients will be required to complete the dose escalation portion of the study.
The Phase 2 portion of the study will be carried out exclusively in FLC patients up to 39 years old. DT2216 will be administered at the recommended dose established in Phase 1, together with irinotecan at its standard dose. Its main goal will be to define anti-tumor activity of the DT2216/irinotecan combination in FLC patients. Between 8 and 15 patients will be enrolled in this phase.
Trial contact information:
- Children’s Oncology Group: CTGOV_Registration@childrensoncologygroup.org
Please visit clinicaltrials.gov for a more comprehensive list of active trials.
The Fibrolamellar Cancer Foundation does not provide medical advice. We provide website users with information to help them better understand their health conditions and current approaches towards diagnosis, treatment and supportive care. Always seek the advice of your physician or other qualified healthcare provider.