A peptide-based vaccine called mKRAS-VAX has generated durable immune responses against pancreatic cancer in people at hereditary high risk, according to phase 1 trial results published in the American Association for Cancer Research‘s journal Cancer Discovery on 16 July. The mKRAS-VAX pancreatic cancer vaccine was found to be safe in humans and produced T-cell responses that persisted for two years, offering an early proof of concept for a prevention-focused approach to one of the hardest cancers to treat.
What the mKRAS-VAX trial set out to do
Pancreatic ductal adenocarcinoma often develops slowly, over many years, from precursor conditions such as pancreatic cysts. That extended window is precisely where researchers at the Johns Hopkins Kimmel Cancer Center and its Skip Viragh Center for Pancreatic Cancer saw an opportunity: could the immune system be trained to recognise and destroy abnormal cells before they become cancer?
KRAS mutations are present in most pancreatic cancers and in most pancreatic precancerous lesions, making the gene a logical target. The mKRAS-VAX vaccine, developed at Johns Hopkins, uses a mix of peptides and an immuno-adjuvant to prompt that immune recognition. According to Johns Hopkins Medicine, the vaccine targets the six most common KRAS mutations found in pancreatic cancer, broadening its potential reach across the patient population.
Twenty participants with a hereditary predisposition to pancreatic cancer and a pancreatic abnormality identified through imaging received the drug between April 2022 and February 2026. Each participant received four doses over 13 weeks. Researchers monitored safety and immune responses through blood testing and follow-up evaluations.
Results from the mKRAS-VAX pancreatic cancer vaccine trial
18 of the 20 participants, or 90%, developed a median 18-fold increase in mutant KRAS-specific T-cell responses, indicating that the vaccine successfully activated immune cells capable of recognising KRAS mutations. Crucially, that response did not fade quickly: additional analyses showed it persisted for two years before monitoring concluded.
After a median follow-up of 16.5 months, none of the participants developed pancreatic cancer or a high-risk pancreatic lesion requiring surgical removal. All treatment-related adverse events were classified as mild to moderate. The most common side effects were injection-site reactions, fatigue, chills, and flu-like symptoms, all of which resolved without requiring treatment.
Elizabeth Jaffee, the Dana and Albert “Cubby” Broccoli Professor of Oncology and co-director of the Skip Viragh Center for Pancreatic Cancer, was co-senior author of the study. ‘This is just the beginning, but the findings suggest that the immune system is getting activated,’ she said. ‘We have more work to do, but this is a good start aimed at prevention, which no one had thought about doing before.’
Context, caveats and what came before
The investigators are clear about the limits of what this trial can demonstrate. The study was designed primarily to evaluate safety and immune responses, and was not intended to determine whether the drug prevents pancreatic cancer. The small study size and relatively short follow-up period limit conclusions about clinical efficacy, the researchers caution.
Those caveats are real. Twenty participants is a small cohort, and pancreatic cancer can take many years to develop from precursor lesions, meaning that a median follow-up of 16.5 months cannot settle questions about long-term prevention. The investigators frame this as a necessary first step, not a finished answer.
There is, however, earlier data that gives context to the immune response results. The mKRAS approach was first tested in 2020 in patients who had undergone surgery and were at high risk of cancer recurrence. A study of those results, published in Nature Communications in 2026, found that when the drug generated a strong immune response, those patients remained disease-free for at least five years. The new phase 1 trial is described by its developers as the first-in-human demonstration for a drug aimed at preventing pancreatic cancer in people with a high-risk KRAS mutation, rather than treating it after surgery.
The full findings are published in Cancer Discovery. The next stage will need a larger cohort and a longer follow-up to determine whether the immune activation seen here translates into a measurable reduction in cancer development, a question the investigators say they intend to pursue.
