Results from a Phase I clinical trial show early promise for a vaccine designed to prevent pancreatic cancer in people at high risk of developing the disease.
Pancreatic cancer is often diagnosed at advanced stages and grows rapidly, contributing to its poor survival rates.
The Phase I clinical trial evaluated the mKRAS-VAX vaccine in 20 participants with genetic predisposition to pancreatic cancer and a pancreatic abnormality identified through imaging.
None of the patients developed pancreatic cancer or high-risk lesions during the study, and 90% of them developed a significant immune response to the vaccine.
If successful in larger clinical studies, the vaccine could offer the first interception strategy to reduce the number of pancreatic cancer cases.
Results from a Phase I clinical trial show early promise for a vaccine designed to prevent pancreatic cancer in people at high risk of developing the disease. Published in Cancer Discovery, the findings suggest it may be possible to intercept one of the most aggressive forms of cancer before it takes hold.
Pancreatic cancer is often diagnosed at advanced stages and grows rapidly, contributing to its poor survival rates. Yet the disease typically develops over many years from pancreatic cysts and other precursor lesions, creating a window of opportunity to intervene before those lesions turn into malignant tumors.
“Individuals at high risk due to hereditary predisposition or to the presence of a concerning pancreatic lesion detected on imaging usually undergo surveillance to monitor for changes over time,” said Neeha Zaidi, MD, associate professor of oncology at Johns Hopkins Medicine and co-senior author of the study. “If there is a high enough concern for transformation to cancer or if early cancer is detected, the current standard of care is surgical resection. However, the chances of recurrence are up to 80%, and many precursor lesions to pancreatic cancer are microscopic and thus undetectable by imaging.”
More than 90% of pancreatic cancers are driven by mutations in the KRAS gene, which also appear in many precancerous lesions. Zaidi’s team developed a vaccine targeting the six most common KRAS mutations, with the goal of training the immune system to recognize and attack cells carrying these mutations before they become cancerous.
The Phase I clinical trial evaluated the mKRAS-VAX vaccine in 20 participants with genetic predisposition to pancreatic cancer and a pancreatic abnormality identified through imaging. Patients received four doses of the vaccine over the course of 13 weeks and were monitored for side effects and immune responses for a median follow-up time of 16.5 months.
None of the patients developed pancreatic cancer or high-risk lesions during the study, and 90% of them developed a significant immune response to the vaccine. Memory cells against the six KRAS mutations were still detectable in the blood for as long as two years after vaccination.
“This long-lasting response is particularly noteworthy when assessing for possible interception of cancer, which requires long-lasting immunity,” said Zaidi. “In addition, the vaccine was safe and well tolerated, supporting its use in larger cancer interception studies.”
Although the main goal of the study was to prove the vaccine’s safety, an exploratory imaging analysis found that pancreatic cysts completely regressed in five participants and partially regressed in three, while the remaining remained stable.
The vaccine had previously been tested in pancreatic cancer patients who had undergone surgery and were at high risk of experiencing recurrence, where all participants remained disease free for at least five years. “We thought if we can see an immune response in patients with cancer, the vaccine should work even better in people who are at higher risk because of a family history, gene alteration or cyst on the pancreas,” said Zaidi.
Another trial is currently enrolling patients to study whether the immune response generated by the vaccine can infiltrate within precancerous lesions in addition to being detectable in the blood. If successful in larger clinical studies, the vaccine could offer the first interception strategy to reduce the number of pancreatic cancer cases.
“Prevention and interception save lives and reduce the morbidity associated with cancer development and progression. This is especially important for cancers whose early-onset frequency is increasing and for which we do not have effective methods for early detection,” says Elizabeth Jaffee, MD, deputy director of the Johns Hopkins Kimmel Cancer Center, co-director of the Skip Viragh Center for Pancreatic Cancer, and associate director of the Bloomberg~Kimmel Institute for Cancer Immunotherapy.
“This is just the beginning, but the findings suggest that the immune system is getting activated. We have more work to do, but this is a good start aimed at prevention, which no one had thought about doing before.”
