Novel Vaccine Shows Early Responses in Pancreatic Cancer and CRC

"Taken together, the long-term follow-up of the phase 1 AMPLIFY-201 study provides evidence that ELI-002 2P induces potent, polyfunctional [CD4-positive] and [CD8-positive] T cell immunity to [KRAS mutations] alongside frequent antigen spreading that may delay tumor recurrence," according to the study authors.

A vaccination of ELI-002 2P produced immune responses that may correlate with delayed tumor recurrence in a small cohort of patients with KRAS-mutated pancreatic ductal adenocarcinoma (PDAC) or colorectal cancer (CRC), according to findings from the phase 1 AMPLIFY-201 trial (NCT04853017) published in Nature Medicine.¹

With a median follow-up of 19.7 months and a data cutoff of September 24, 2024, updated findings showed no new safety signals. Treatment with ELI-002 2P yielded a median overall survival (OS) of 28.94 months, and the median radiographic relapse-free survival (RFS) was 15.31 months. Within the PDAC subgroup (n = 20), the median RFS and OS were 15.31 months and 28.94 months, respectively.

Data showed KRAS mutation-specific T cell responses in 84% of patients after treatment with ELI-002 2P, with a median response that was 13.38 times higher than baseline for all patients. Additionally, 71% of patients had induced responses of both CD4-positive and CD8-positive KRAS mutation-specific T cells, which significantly corresponded with overall tumor biomarker response. The median OS among patients with T cell responses above a threshold of 9.17 was not reached vs 15.98 months in those without (HR, 0.23; P = .0099). Furthermore, the median RFS was not reached in those with above-threshold T cell responses, and 3.02 months for those with T cell fold changes above or below the threshold (HR, 0.12; P = .0002).

“Taken together, the long-term follow-up of the phase 1 AMPLIFY-201 study provides evidence that ELI-002 2P induces potent, polyfunctional [CD4-positive] and [CD8-positive] T cell immunity to [KRAS mutations] alongside frequent antigen spreading that may delay tumor recurrence,” lead study author Zev A. Wainberg, MD, MSc, a professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA) and researcher in the UCLA Health Jonsson Comprehensive Cancer Center, wrote with coauthors in the publication.¹ “A randomized phase 2 study [NCT05726864] of a 7-peptide formulation [of (ELI-002 7P]…is ongoing in the adjuvant setting of PDAC.”

In this first-in-human phase 1 study, patients with stage I to IV oligometastatic PDAC or high-risk stage II to IV oligometastatic CRC (n = 5) were assigned to undergo immunization with ELI-002 2P. Investigators administered fixed doses of Amph-Peptides 2P G12D and G12R at 0.7 mg each with escalating doses of adjuvant Amph-CpG-7909 at 0.1 mg, 0.5 mg, 2.5 mg, 5.0 mg, and 10.0 mg. The study treatment occurred as part of a prime immunization series including 6 subcutaneous doses of ELI-002 2P over 8 weeks, a no dosing period for 3 months, and a booster immunization series consisting of 4 weekly doses. Investigators also monitored safety and efficacy outcomes in patients for up to 2 years after the initial dose.

The trial’s primary end points were safety, tolerability, and the recommended phase 2 dose. Secondary and exploratory end points included tumor biomarker reduction and clearance, radiographic RFS, OS, and immunogenicity.

Patients 18 years and older with KRAS- or NRAS-mutated solid tumors, circulating tumor DNA positivity and/or elevated serum tumor biomarkers even after prior standard therapy consisting of surgery and chemotherapy or radiation, where applicable, a negative CT result for recurrent disease, and an ECOG performance status of 0 or 1 were eligible for enrollment.² Those with tumor mutations for which specific therapy was already approved, known brain metastases, or use of immunosuppressive agents were unable to enroll.

“Beyond PDAC, off-the-shelf availability of ELI-002 supports broad development for various [KRAS mutation]-expressing tumor types. In conclusion, our observations support continued study of amphiphile lymph node-targeted immunotherapy for solid tumors,” the study authors wrote.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. Published online August 11, 2025. doi:10.1038/s41591-025-03876-4
2. A study of ELI-002 in subjects with KRAS mutated pancreatic ductal adenocarcinoma (PDAC) and other solid tumors (AMPLIFY-201). ClinicalTrials.gov. Updated January 17, 2025. Accessed August 12, 2025. https://tinyurl.com/4pchsusf