Journal article
Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results
Nature medicine, Vol.31(11), pp.3648-3653
11/2025
DOI: 10.1038/s41591-025-03876-4
PMCID: PMC12618236
PMID: 40790272
Abstract
Cellular immunity, mediated by tumor antigen-specific CD4+ and CD8+ T cells, has a critical role in the success of cancer immunotherapy by targeting intracellular driver and passenger tumor mutations. We present the final results of the phase 1 AMPLIFY-201 trial, in which patients who completed standard locoregional treatment, with minimal residual mKRAS disease (n = 25, 20 pancreatic cancer and 5 colorectal cancer), received monotherapy vaccination with lymph node-targeting ELI-002 2P, including mutant KRAS (mKRAS) amphiphile-peptide antigens (G12D, G12R) and amphiphile-adjuvant CpG-7909. At a median follow-up of 19.7 months, efficacy correlated with mKRAS-specific T cell responses above or below a threshold 9.17-fold increase over baseline, with median radiographic relapse-free survival not reached, versus 3.02 months (hazard ratio (HR) = 0.12, P = 0.0002) and median overall survival not reached versus 15.98 months (HR = 0.23, P = 0.0099). Seventy-one percent of evaluable patients induced both CD4+ and CD8+ subsets, with sustained immunogenicity. Following ELI-002 2P treatment, antigen spreading was observed in 67% of patients, with increased T cells reactive to personalized, tumor antigens absent from the ELI-002 2P vaccine. Therefore, lymph node-targeting amphiphile vaccination induces persistent T cell responses targeting oncogenic driver KRAS mutations, alongside personalized, tumor antigen-specific T cells, which may correlate to clinical outcomes in pancreatic and colorectal cancer. ClinicalTrials.gov registration: NCT04853017.
Details
- Title: Subtitle
- Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results
- Creators
- Zev A Wainberg - University of California, Los AngelesColin D Weekes - Massachusetts General HospitalMuhammad Furqan - University of IowaPashtoon M Kasi - University of IowaCraig E Devoe - Northwell HealthAlexis D Leal - University of Colorado DenverVincent Chung - City Of Hope National Medical CenterJames R Perry - Elicio Therapeutics, Boston, MA, USAThian Kheoh - Elicio Therapeutics, Boston, MA, USALisa K McNeil - Elicio Therapeutics, Boston, MA, USAEsther Welkowsky - Elicio Therapeutics, Boston, MA, USAPeter C DeMuth - Elicio Therapeutics, Boston, MA, USAChristopher M Haqq - Elicio Therapeutics, Boston, MA, USA. chris.haqq@elicio.comShubham Pant - The University of Texas MD Anderson Cancer CenterEileen M O'Reilly - Memorial Sloan Kettering Cancer Center
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.31(11), pp.3648-3653
- DOI
- 10.1038/s41591-025-03876-4
- PMID
- 40790272
- PMCID
- PMC12618236
- NLM abbreviation
- Nat Med
- ISSN
- 1078-8956
- eISSN
- 1546-170X
- Publisher
- NATURE PORTFOLIO
- Grant note
- Elicio Therapeutics
The study was sponsored and funded by Elicio Therapeutics. We thank the patients and their caregivers and families for their participation in this study, the physicians, nurses and site staff who cared for the patients and supported the study. Employees of Elicio Therapeutics received salaries for their contributions to the study. Aside from grants to their institutions, no other authors received specific funding for this work.
- Language
- English
- Electronic publication date
- 08/11/2025
- Date published
- 11/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984946697002771
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