An experimental cancer vaccine from the Johns Hopkins Kimmel Cancer Center and the Bloomberg~Kimmel Institute for Cancer Immunotherapy has delivered encouraging results in a phase I trial for fibrolamellar carcinoma (FLC), a rare liver cancer that predominantly affects adolescents and young adults. Supported by the National Cancer Institute and the Fibrolamellar Cancer Foundation, the study, conducted with St. Jude Children’s Research Hospital and reported by Johns Hopkins Medicine, reported disease control in 75% of evaluable patients and deep, potentially curative responses in 25%.
Among 12 fully evaluable participants (median age 23) whose tumors were initially unresectable and largely resistant to prior chemotherapy, nine achieved stable disease or measurable immune responses. Three patients are now believed to be cancer-free, including a 13-year-old who had an almost complete response and continued on immunotherapy for two years. In one case, the vaccine plus immunotherapy converted an inoperable tumor into a surgical candidate, enabling successful resection and rapid symptom relief within months of enrollment. Results were published Nov. 24 in Nature Medicine.
FLC’s biology makes it uniquely suited to vaccine strategies. Nearly all cases share a single oncogenic driver: a DNAJB1–PRKACA fusion protein. This uniform target enabled development of a single, “universal” vaccine designed to train the immune system against a cancer-specific hallmark across patients, explained co-corresponding author Mark Yarchoan, M.D. Lead author Marina Baretti, M.D., emphasized the unmet need: there are no FDA-approved standard treatments for FLC, and outcomes are particularly poor when tumors cannot be surgically removed, despite patients typically being otherwise healthy.
From April 2020 to September 2022, 16 patients aged 12 and older were enrolled: four discontinued for various reasons. The protocol included a 10-week priming phase, weekly vaccine injections for one month, then every three weeks, followed by maintenance dosing every eight weeks for up to a year. Concurrently, patients received immune checkpoint inhibitors used in other liver cancers: two agents every three weeks during priming (four doses total), then monthly for up to two years, to bolster antitumor immunity.
Safety was favorable. The most common side effects were injection-site reactions, headache, and fatigue, with the regimen overall well tolerated for this high-need population.
Investigators are expanding enrollment while planning a larger clinical trial to validate efficacy and durability. The work reflects a multi-institution effort, with co-authors from Johns Hopkins, St. Jude, and the Fibrolamellar Cancer Foundation. Funding came from the National Institutes of Health (R01-CA265009, P30 CA006973), the Fibrolamellar Cancer Foundation, an ASCO Career Development Award, BSM Rare Cancers, the TIRTL Blue Sky Initiative, and ALSAC at St. Jude.
For patients and families facing FLC, these early data suggest a new therapeutic avenue: a well-tolerated, precision vaccine built around a shared tumor driver that can stabilize disease, deepen responses, and, in some cases, enable surgery or achieve apparent remission. As Yarchoan noted, seeing patients reach major life milestones after treatment underscores the potential impact of this targeted immunotherapy approach.
