Experimental Drug Triggers Immune Response Against Pancreatic Cancer in High-Risk Individuals

Researchers at the Johns Hopkins Kimmel Cancer Center and its Skip Viragh Center for Pancreatic Cancer have reported results from a first-in-human phase 1 clinical trial of an experimental drug designed to prevent pancreatic cancer in people at high genetic risk. The findings were published July 16 in Cancer Discovery, a journal of the American Association for Cancer Research.

The drug targets mutant KRAS, a genetic driver present in most pancreatic cancers and precancerous lesions. It uses a mixture of peptides and an immuno-adjuvant to train the immune system to recognize and destroy cells carrying the mutation before they progress to cancer, functioning similarly to a vaccine.

Twenty participants with a hereditary predisposition to pancreatic cancer and a pancreatic abnormality detected by imaging enrolled in the trial between April 2022 and February 2026. Each received four doses over 13 weeks, with safety and immune responses monitored through blood tests and follow-up evaluations.

Eighteen of the 20 participants, or 90%, developed a median 18-fold increase in mutant KRAS-specific T-cell responses, indicating successful activation of immune cells capable of recognizing the mutation. Additional analyses showed this immune response persisted for two years until monitoring concluded.

After a median follow-up of 16.5 months, none of the participants had developed pancreatic cancer or a high-risk lesion requiring surgical removal. All treatment-related adverse events were classified as mild to moderate, including injection-site reactions, fatigue, chills, and flu-like symptoms that resolved without treatment.

The investigators emphasized that the study was designed primarily to evaluate safety and immune response, not to determine whether the drug prevents cancer. They cautioned that the small sample size and relatively short follow-up period limit conclusions about clinical efficacy.

Previous research published in Nature Communications in 2026 tested the same KRAS immune treatment in patients who had undergone surgery and were at high risk of recurrence. In that study, patients who generated a strong immune response remained disease-free for at least five years.

Elizabeth Jaffee, MD, deputy director of the Kimmel Cancer Center and co-senior author, described the current findings as a good start aimed at prevention, an approach that had not been attempted before for this cancer type.