Combination Therapy for Fibrolamellar Carcinoma

This trial tests a new combination of treatments to determine if they can safely combat fibrolamellar carcinoma, a rare liver cancer. The trial involves a special vaccine (DNAJB1-PRKACA Peptide Vaccine) and three other drugs to assess their ability to shrink tumors and extend the time patients live without cancer progression. Individuals with this specific cancer type, which has spread or cannot be surgically removed, and whose cancer has advanced despite prior immunotherapy, may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

The trial requires that you stop taking certain medications, such as chemotherapy, biological cancer therapy, or radiation, at least 14 days before starting the study drug. Additionally, if you are taking potent inducers of CYP 3A4/5, you must safely discontinue them at least 14 days before the trial begins.

Research has shown that the DNAJB1-PRKACA peptide vaccine is initially safe. In earlier studies, patients tolerated it well when combined with treatments like nivolumab and ipilimumab, though some manageable side effects occurred.

For DRP-104, studies found it to be generally well-tolerated when used with other drugs. This treatment alters how cancer cells use nutrients, potentially enhancing the immune system's ability to fight tumors.

Ipilimumab and nivolumab have FDA approval for treating other cancers and have a history of safety. Common side effects include tiredness and changes in liver function tests, but these are usually manageable.

Unlike the standard treatments for fibrolamellar carcinoma, which often include surgery, chemotherapy, and targeted therapy, the combination therapy under study takes an innovative approach. This treatment uses a unique DNAJB1-PRKACA peptide vaccine with a poly-ICLC adjuvant, which aims to stimulate the immune system in a new way. Additionally, it includes DRP-104, a novel compound designed to inhibit tumor metabolism, along with the immune checkpoint inhibitors nivolumab and ipilimumab, which help the immune system recognize and attack cancer cells more effectively. Researchers are excited because this multi-faceted approach could potentially offer a more targeted and robust attack against cancer cells, possibly improving outcomes for patients with this challenging condition.

Research has shown that the DNAJB1-PRKACA peptide vaccine may help treat fibrolamellar carcinoma, a rare type of liver cancer. In one study, 19% of patients experienced a noticeable decrease in tumor size, and 62.5% had their disease stabilize. DRP-104, which targets how tumors use energy, demonstrated strong anti-tumor effects in earlier research, especially when combined with other treatments. The immunotherapy drugs Ipilimumab and Nivolumab have also shown some success in shrinking tumors and improving survival in similar cancers. This trial will administer a combination of these treatments, including the DNAJB1-PRKACA peptide vaccine with poly-ICLC adjuvant, DRP-104, Nivolumab, and Ipilimumab, to leverage the strengths of each in combating this challenging disease.¹²³⁵⁶