A phase 1 trial suggests off-the-shelf immunotherapy could boost recurrence-free survival.
A peptide-based cancer vaccine targeting mutant KRAS has shown encouraging results in prolonging recurrence-free survival for patients with pancreatic or colorectal cancer, according to phase 1 trial findings published in Nature Medicine.
The investigational vaccine, ELI-002 2P, is designed to deliver mutant KRAS peptides directly to lymph nodes to prime T cells against cancer cells. Unlike personalised vaccines, it is manufactured in bulk and can be used off-the-shelf, offering potential scalability.
In the single-arm trial, 25 patients (20 with pancreatic cancer, five with colorectal cancer) who had completed surgery and chemotherapy but had residual cancer signals in the blood received ELI-002 2P.
After a median follow-up of almost 20 months, 68% developed robust mutant KRAS–specific T cell responses. Those with stronger responses had significantly longer recurrence-free and overall survival.
For pancreatic cancer, median overall survival approached 29 months, with median recurrence-free survival exceeding 15 months, both surpassing historical controls.
Notably, some patients mounted immune responses not only to the KRAS mutations in the vaccine but also to additional tumour-specific KRAS mutations, hinting at potential for broader immune recognition.
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The US researchers noted that relapse rates remain high in both cancers despite surgery and chemotherapy, underscoring the need for more effective post-treatment strategies. The vaccine is now being assessed in a phase 2 randomised trial to confirm these findings.
If validated, it could represent a new immunotherapeutic option for high-risk patients, harnessing T cell–mediated immunity against one of the most common and challenging cancer mutations.
“Recently, multiple examples of next-generation therapeutic cancer vaccination have demonstrated promise in early phase and randomised clinical studies,” the researchers wrote.
“Innovative trial designs have focused on the adjuvant setting, where tumour burden is low, potentially allowing for robust and durable T cell responses to provide long-term protection from recurrence and death.
“Historically, PDAC [pancreatic ductal adenocarcinoma] has previously been considered a poor setting for immunotherapy; however, the favourable results from ELI-002 2P are consistent with the long-term follow-up of adjuvant patients with PDAC who received personalised mRNA vaccination in combination with atezolizumab and adjuvant mFOLFIRINOX.”
The researchers noted that in the majority of T cell responders (17 out of 21), T cell responses were observed against the specific tumour antigen detected at the time of enrolment.
“Analysis of tumour-specific T cell response and antigen spreading among larger patient groups, and with additional serial PBMC samples, will be helpful to further understand the instances where responses to the tumour antigen identified during screening were not observed,” they said.
“Additional longitudinal data will be useful to inform whether long-term dosing may augment cellular immunity.”
