KRAS-Targeted Vaccine Shows Durable Immune Responses, Survival Benefits in Pancreatic Colorectal Cancers

ELI-002 2P (Elicio Therapeutics), an off-the-shelf KRAS-targeting cancer vaccine, demonstrated significant improvements in survival outcomes in patients with resected pancreatic and colorectal cancers (CRC), according to data from a phase 1 trial (NCT04853017). Although the data is in its infancy, the investigators report robust immune responses and evidence of sustained disease control.

Pharmacist drawing vaccine from vial | Image Credit: © Alernon77 - stock.adobe.com

The results, published in Nature Medicine, are from the open-label, dose-escalation, phase 1 AMPLIFY-201 trial evaluating the safety and efficacy of ELI-002 2P immunotherapy. ELI-002 2P is an investigational vaccine designed to target mutant KRAS proteins. It uses an amphiphile delivery platform to direct 2 KRAS peptide antigens (G12D and G12R) to lymph nodes by binding to albumin in the blood. This “albumin hitchhiking” allows them to efficiently traffic to lymph nodes, where immune activation occurs.^1,2

“Basically, the vaccine hitches a ride on the albumin directly to the lymph nodes,” Shubham Pant, MD, MBBS, of the University of Texas MD Anderson Cancer Center, lead investigator, said in a news release. “This leads to a more robust immune response because the peptides aren’t just circulating freely in the blood—they are presented directly to the lymph nodes.”²

The trial enrolled 25 patients, of which 20 had pancreatic ductal adenocarcinoma (PDAC) and 5 had CRC across 7 US centers between October 2021 and September 2024. All participants completed surgery and chemotherapy but remained at high risk for relapse due to minimal residual disease (MRD) detected by circulating tumor DNA (ctDNA) or elevated tumor biomarkers. The median patient age was 61, 60% were women, and 84% were white. The primary end point was the safety of ELI-002, with secondary end points involving ctDNA reduction or clearance.¹

After a median follow-up of 19.7 months, the median relapse-free survival (RFS) for the entire cohort was 16.3 months, and the median overall survival (OS) reached 28.9 months. In the pancreatic cancer subgroup, median RFS was 15.3 months, and OS was also 28.9 months. Historically, PDAC patients with ctDNA-positive MRD relapse quickly post-surgery, often within months.¹

KRAS mutation-specific T-cell responses were induced in 21 of 25 patients, with 59% exhibiting both CD4+ and CD8+ activity. A key finding was the strong correlation between the magnitude of T-cell response and clinical benefit. Using a predefined threshold of a 9.17-fold increase in KRAS-specific T cells over baseline. The investigators separated patients into high- (n = 17) and low-response (n = 8) groups.¹

In the high-response group, median RFS and OS were not reached, compared with 3.02 and 15.98 months, respectively, for the low-response group. Eleven high responders remained free of radiographic progression at the last follow-up, including 5 who required no additional therapy after vaccination. Six achieved complete ctDNA clearance. In contrast, all low responders experienced disease progression, and 7 died.¹

Immunologic analyses showed the vaccine elicited both CD4+ helper and CD8+ cytotoxic T-cell responses, with evidence of antigen spreading in two-thirds of patients. Safety results were favorable: treatment-related adverse events occurred in 48% of patients, all grade 1 or 2, with no grade 3 or higher events, cytokine release syndrome, or dose-limiting toxicities.¹

“It’s early, but the results look promising,” Pant said in the news release. “These patients got robust T-cell responses, and the majority have not recurred.”²

If validated in larger, randomized trials, KRAS-targeted vaccination could become a new approach for preventing recurrence in some of the most aggressive solid tumors.¹

REFERENCES

1. Wainberg ZA, Weekes CD, Furqan M, et al. Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results. Nat Med. August 11, 2025. doi:10.1038/s41591-025-03876-4

2. Bassett M. Novel vaccine shows promise in pancreatic cancer. MedPage Today. August 13, 2025. Accessed August 13, 2025. https://www.medpagetoday.com/hematologyoncology/othercancers/116973