Pancreatic cancer is notoriously difficult to treat, but an experimental vaccine may offer a new way to target mutations that drive the disease. Results from a phase 2 clinical trial showed a strong immune response among nearly every vaccinated patient, although the treatment did not significantly improve disease free survival.

The vaccine, called camupepimut, trains the immune system to recognize and respond to seven mutations in the KRAS gene. These mutations occur in about 90% of pancreatic ductal adenocarcinomas and help drive cancer growth.

Camupepimut was designed to deliver its key ingredients directly to the lymph nodes, where immune responses are mounted. Its ingredients are attached to a fatty molecule that binds to the blood protein albumin, which then carries them efficiently into the lymph nodes.

That approach is intended to confront a particularly stubborn cancer. Pancreatic cancer carries a high risk of returning after surgery and chemotherapy because it can spread rapidly.

Scientists led by Mayo Clinic researchers examined whether the vaccine could help the immune system find and destroy cancer cells that remained hidden in the body after treatment. Their trial included 144 patients with pancreatic cancer involving KRAS mutations.

All participants had undergone surgery and chemotherapy and showed no detectable signs of cancer. Through random selection, 96 patients received camupepimut, while the other 48 were observed without receiving the vaccine.

The vaccine did not produce a statistically significant improvement in disease free survival. The average was 23.8 months among vaccinated patients, compared with 21.2 months in the observation group.

Despite that result, the immune findings offered a measure of hope. Nearly 99% of patients who received the vaccine developed increased T-cell responses against mutated KRAS.

T-cells are white blood cells with an important role in the immune system. The response also persisted, with 95.5% of vaccinated patients showing detectable T-cell responses to the KRAS mutations more than 46 weeks after the study began.

Researchers believe that durable response indicates that camupepimut still holds promise. The trial also produced clues that could help identify which patients may benefit most from the experimental vaccine.

One clue involved circulating tumor DNA, also known as ctDNA, which consists of small pieces of DNA released by cancer cells. Patients who had no detectable ctDNA in their blood at the beginning remained free of cancer longer with the vaccine than those without.

The researchers also found that participants who had not received radiotherapy had more lymphocytes. Those patients appeared to respond better to the vaccine, giving scientists another factor to consider as they refine the treatment and plan a larger phase 3 clinical trial.

“The immune response is an important signal that helps us understand what is happening biologically and gives us important information for the next trial,” lead study author Ben George, a medical oncologist at the Mayo Clinic, said in a statement.

“What is encouraging is that we were able to generate a strong immune response against KRAS mutations in nearly every patient we evaluated. In an exploratory analysis, patients with greater immune responses to the vaccine appeared protected with longer disease-free survival times,” he added.

Other experimental pancreatic cancer vaccines are also being developed. One project that reported early findings in April is using mRNA technology to deliver personalized vaccines to people with aggressive forms of the disease.

The search for new approaches comes as pancreatic cancer cases rise worldwide. Global incidence more than doubled over three decades, increasing from about 196,000 new cases in 1990 to more than 510,000 in 2022.

More cases are also affecting younger adults, particularly younger women, for reasons that are not yet fully understood. The camupepimut trial was published in the journal Nature Medicine.