We are pleased to announce that FCF has awarded Dr. Marina Baretti and Dr. Mark Yarchoan of Johns Hopkins University a grant to launch a new clinical trial for FLC patients. Both investigators have extensive experience in treating patients with FLC and in the development of immunotherapies. They already have collaborated closely on the clinical testing of a peptide vaccine targeting the DNAJB1-PRKACA fusion protein that drives the disease.

This new study, named Exploiting a Critical Vulnerability to Glutamine Antimetabolite Therapy in Fibrolamellar Hepatocellular Carcinoma (FLC), will test a new cancer treatment that capitalizes on FLC’s unique metabolism.

Recent work from several research teams indicates that the DNAJB1-PRKACA fusion causes a metabolic rewiring of FLC tumor cells that makes them dependent on breaking down large amounts of the amino acid glutamine. This “glutamine addiction” leads to a nutrient-depleted tumor environment that is also enriched in immunosuppressive metabolites including ammonia. This could impair a patient’s ability to launch an effective immune response to the cancer.

Based on these findings, the JHU team plans to test the effectiveness of treating FLC patients with an inhibitor of glutamine metabolism (DRP-104; sirpiglenastat) in combination with an immune checkpoint inhibitor (durvalumab). The team’s hypothesis is that this treatment could deliver a “one-two punch” against FLC by:

• Directly attacking an important metabolic pathway of FLC tumors
• Restoring an immune supportive tumor environment, and therefore enabling a patient’s immune cells to attack the cancer.

The drug DRP-104 is being developed by Dracen Pharmaceuticals. Initial testing of DRP-104 in patients with solid tumors has already been completed. Dracen will provide DRP-104 for this FLC trial, as well as the necessary regulatory and operational support for the effort.

The phase 1b/2 clinical trial at Johns Hopkins will enroll patients diagnosed with unresectable or metastatic FLC whose disease progressed on prior immune therapy. If successful, this treatment could eventually be combined with other approaches, including targeted therapies, immune cell therapies and therapeutic vaccines.

The new trial is currently in a detailed planning phase. Patient enrollment is anticipated to begin in late 4Q 2023. More information will be released once the trial receives all the necessary institutional and regulatory approvals.