Novel liver cancer vaccine achieves responses in rare disease affecting children and young adults

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An experimental cancer vaccine developed at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Institute for Cancer Immunotherapy has shown early promise in a phase I clinical trial for a rare form of liver cancer that primarily affects children and young adults. The trial, led by investigators at Johns Hopkins and St. Jude Children’s Research Hospital, was supported by the National Cancer Institute and the Fibrolamellar Cancer Foundation.

In the study, 75% of participants (nine patients) with fibrolamellar carcinoma (FLC) experienced disease control, including stable disease or measurable immune responses. Three patients (25%) had deep responses and are now believed to be cancer-free, including a 13-year-old who achieved a nearly complete response and continued on immunotherapy for two years.

These findings will be published on Nov. 24 in Nature Medicine.

Most of the patients had tried at least one prior chemotherapy treatment and failed to respond. In one patient, treatment with the vaccine and immunotherapy allowed for successful surgical removal of the tumor. Prior to the therapy, the patient had been in significant pain, and symptom-directed care had been considered. This study provided a much-needed treatment option for the patient, and resulted in a response within a few months of being enrolled in the trial.

“This was a remarkable outcome,” says co-corresponding study author Mark Yarchoan, M.D., an associate professor of oncology at the Johns Hopkins University School of Medicine. “To see patients achieve such deep and lasting responses, and reach important life milestones, was incredibly encouraging.”

FLC is a rare liver cancer that affects approximately 500 people each year in the United States, typically healthy adolescents and young adults, explains lead study author Marina Baretti, M.D., an assistant professor of oncology at the Johns Hopkins University School of Medicine and the Jiasheng Chair in Hepato-Biliary Cancer Research.

“When most people think of liver cancer, they think of cirrhosis or hepatitis,” Baretti says. “But for this pediatric and young adult cancer, most patients are otherwise healthy. Unfortunately, there are no FDA-approved standard treatments, and the prognosis is especially poor for those whose tumors cannot be surgically removed.”

What makes FLC uniquely suited for vaccine therapy is the presence of a consistent cancer driver in all patients: a fusion of the DNAJB1 and PRKACA proteins. This fusion protein creates a target shared by all FLC tumors, allowing for a single, universal vaccine that can potentially be used to treat patients with this cancer, Yarchoan explains.

From April 2020 to September 2022, investigators enrolled 16 patients age 12 and up, all with FLC that could not be surgically removed. The median patient age was 23. Four discontinued treatment for different reasons, leaving 12 for full evaluation.

There were two phases of the study: a 10-week priming phase and a maintenance phase of up to two years. During priming, patients received injections of the vaccine once a week for the first month, and then once every three weeks. During maintenance, they received the vaccine every eight weeks for up to a year. Along with the vaccine, they received intravenous infusions of immune checkpoint inhibitor drugs that are used for other liver cancers, to stimulate the immune system. During priming, they received two different immune therapies once every three weeks for a total of four times, followed by once a month for up to two years.

Overall, the vaccine was well-tolerated. The most common adverse events were injection-site reactions, headaches and fatigue.

Investigators are now expanding the study to allow treatment of more patients while they plan a larger clinical trial.

Study co-authors were Brian H. Ladle, Kayla J. Bendinelli, Zeal Kamdar, Won Jin Ho, Hao Wang, Heng-Chung Kung, Jeric Hernandez, Hanfei Qi, Sarah M. Shin, Alexei Hernandez, Mari Nakazawa, Robert A. Anders, Chris Thoburn, Neeha Zaidi, Amanda L. Huff, Mark Furth, Julie Nauroth and Elizabeth Jaffee of Johns Hopkins. Additional authors were from St. Jude Children’s Research Hospital in Memphis, Tennessee, and the Fibrolamellar Cancer Foundation in Greenwich, Connecticut.

The work was supported by the National Institutes of Health (grants #R01-CA265009 and P30 CA006973), the Fibrolamellar Cancer Foundation, an ASCO Career Development Award, BSM Rare Cancers, the TIRTL Blue Sky Initiative and ALSAC at St. Jude.

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