KRAS Pancreatic Cancer Vaccine Misses Main Goal but Primes T Cells

An off-the-shelf vaccine aimed at the gene mutations behind most pancreatic cancers did not significantly extend the time patients stayed free of disease in a randomised phase 2 trial, its main goal. But nearly every patient tested mounted an immune response against the mutated gene, and those with the strongest responses tended to stay cancer-free for longer.

The trial, AMPLIFY-7P, enrolled 144 people and was published in Nature Medicine on 23 October. The vaccine is camupepimut, also known as ELI-002 7P, and the study was sponsored and funded by its developer, Elicio Therapeutics. In a news release, Mayo Clinic said the trial was led by its researchers and that the findings will help shape a larger phase 3 trial. Elicio presented the results the same day at the ESMO Congress in Madrid.

A vaccine aimed at KRAS

Mutations in the KRAS gene are found in about 90% of pancreatic ductal adenocarcinomas, the most common type of pancreatic cancer, according to Mayo. They help cancer cells grow and survive. Camupepimut targets seven of the most common versions of the mutation. The paper describes it as seven modified KRAS peptides plus an immune-stimulating adjuvant, all built to travel to the lymph nodes, where many immune responses begin.

Unlike personalised vaccines made for one patient’s tumour, this one is “off the shelf”. It is meant for anyone whose tumour carries one of the seven mutations it covers.

How the trial was run

All 144 patients had stage 1 to 3 KRAS-mutated pancreatic cancer and had already had surgery and chemotherapy. None had cancer visible on scans when they joined. They were randomly assigned two to one: 96 received the vaccine and 48 were placed under observation. The trial ran at 24 centres in the US and was open-label, so patients and doctors knew who was receiving the vaccine.

The result on the main goal

The trial missed its primary endpoint. Median disease-free survival, the time patients lived without their cancer returning, was 23.8 months with the vaccine and 21.2 months under observation. The paper gives a hazard ratio of 0.85, well short of the threshold the trial set for success, and Mayo says the difference was not statistically significant. The median follow-up at the data cut-off was 19.4 months. Overall survival results are not yet available.

On safety, the paper reports severe side effects (grade 3 or above) in 10.4% of vaccinated patients against 14.6% of those under observation. Events linked to the vaccine were uncommon and mild, such as dizziness and flu-like illness, and none led to deaths or withdrawal from treatment.

Strong immune signals

The immune results were much stronger. Of the 90 vaccinated patients who could be assessed, 89 developed increased T-cell responses against mutated KRAS. The vaccine switched on both CD4 and CD8 T cells, two key types of immune cell. Among patients assessed at least 46 weeks after the start, 95.5% still had a detectable response. In a small group, the immune system also began recognising other tumour targets that were not in the vaccine.

In an exploratory analysis, patients whose response rose more than about nine-fold over baseline, 74 of 90, had longer disease-free survival than those below that level. “Historically, pancreatic cancer has been very difficult to treat with immunotherapy,” said Dr Ben George, the study’s lead author, whom Mayo describes as a Mayo Clinic medical oncologist. “What is encouraging is that we were able to generate a strong immune response against KRAS mutations in nearly every patient we evaluated.”

Why the subgroup signals need caution

Elicio’s release puts weight on figures that look much better than the headline result. Prespecified subgroups favoured the vaccine, including patients with no tumour DNA in their blood at the start and those who had not had radiotherapy. A post hoc analysis that adjusted for differences between the arms gave a hazard ratio of 0.47. The vaccine arm did start with more patients carrying circulating tumour DNA, a strong predictor of relapse, at 20.8% against 12.5%, while the observation arm had more patients who had received radiotherapy.

Those signals are worth testing, but the paper itself is clear about their limits. The subgroup and immune analyses were not adjusted for multiple comparisons, and the authors call the adjusted analysis “hypothesis generating”. The link between immune response and outcome is also only measured in the vaccinated arm. Patients who respond strongly may differ from weak responders in other ways: those who had received radiotherapy, for example, had fewer lymphocytes and weaker responses. On the question the trial was designed to answer, the vaccine did not clear the bar.

What phase 3 will test

The paper says a phase 3 trial is planned. It suggests that trial should leave out patients who have had radiotherapy, balance patients by tumour DNA status, and consider longer dosing or a combination with checkpoint drugs. Mayo says phase 3 will test whether the vaccine can delay or prevent the cancer returning.

It has been a busy week for cancer immunotherapy. TSN has reported on a personalised mRNA treatment that cut melanoma recurrence, an early NIH-led trial of the T-cell drug invika and an AI tool that spots a DNA-repair defect in ovarian cancer.

“We’ve shown that we can teach the immune system to recognize these KRAS mutations,” Dr George said. “The next step is finding out whether doing that can change the course of the disease for patients.”

TSN collects medical and scientific advances on its Tech for Good hub and in its weekly Tech for Good roundup.

Sources

• Mayo Clinic News Network, “Investigational vaccine generates immune response to KRAS mutations in pancreatic cancer study”, 23 October 2026
• George, B., Singh, H., Devoe, C. E. et al., “Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic cancer: the randomized phase 2 AMPLIFY-7P trial”, Nature Medicine, 23 October 2026
• Elicio Therapeutics, “Elicio Therapeutics Presents Late-Breaking Phase 2 AMPLIFY-7P Results at ESMO Congress 2026 and Announces Simultaneous Publication in Nature Medicine”, 23 October 2026
• ClinicalTrials.gov, NCT05726864 (AMPLIFY-7P)

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