Researchers at Mayo Clinic have made a significant breakthrough in the fight against pancreatic cancer, with an investigational vaccine showing promise in generating an immune response to KRAS mutations. The vaccine, which targets seven of the most common KRAS mutations, was found to help the immune system recognize and respond to these mutations in nearly every patient evaluated.
Targeting KRAS Mutations
Mutations in the KRAS gene are found in about 90% of pancreatic ductal adenocarcinomas, the most common type of pancreatic cancer. The investigational vaccine is designed to travel to the lymph nodes, where it helps T cells recognize and attack altered cells. Unlike some cancer vaccines, this vaccine is “off the shelf” and designed for patients whose tumors have one of the KRAS mutations it targets.
The vaccine activated two important types of T cells, known as CD4 and CD8 T cells, and produced immune responses against several KRAS mutations. In a small group of patients, researchers observed another potentially important effect, known as antigen spreading, where the immune system began recognizing other cancer-related targets that were not included in the vaccine.
Study Results and Next Steps
The study, which included 144 patients with stage 1-3 KRAS-mutated pancreatic cancer, found that 98.9% of patients who received the vaccine developed increased T-cell responses against mutated KRAS. Patients who reached that level of immune response had longer disease-free survival than those who did not.
While the trial did not meet its primary goal of showing an improvement in disease-free survival across the full study population, researchers found other signals that warrant further study. The median disease-free survival was 23.8 months for patients who received the vaccine and 21.2 months for those in the observation group, although the difference was not statistically significant. A phase 3 clinical trial is planned to further study whether the vaccine can delay or prevent pancreatic cancer from returning.
According to Ben George, M.B.B.S, M.D., a Mayo Clinic medical oncologist and lead author of the study, “The immune response is an important signal that helps us understand what is happening biologically and gives us important information for the next trial.” Researchers also found clues that may help predict which patients are more likely to benefit from the vaccine, including the presence of circulating tumor DNA and previous radiation therapy.
In a planned analysis, patients who did not have detectable circulating tumor DNA at the start of the study showed a signal of longer disease-free survival with the vaccine compared with observation. Patients who had received radiation had fewer lymphocytes, a type of white blood cell important to the immune system, and developed weaker KRAS-specific immune responses after receiving the vaccine.
The immune response also persisted over time, with 95.5% of patients still having a detectable KRAS-specific T-cell response at least 46 weeks after the start of the study. As Dr. The study’s results were published in Nature Medicine, and a complete list of authors, disclosures, and funding can be found in the publication.