Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results Journal Article
| Authors: | Wainberg, Z. A.; Weekes, C. D.; Furqan, M.; Kasi, P. M.; Devoe, C. E.; Leal, A. D.; Chung, V. C.; Perry, J. R.; Kheoh, T.; McNeil, L. K.; Welkowsky, E.; Demuth, P. C.; Haqq, C. M.; Pant, S.; O'Reilly, E. M. |
| Article Title: | Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results |
| 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. |
| Keywords: | combination |
| Journal Title: | Nature Medicine |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Publication status: | Online ahead of print |
| Date Published: | 2025-01-01 |
| Online Publication Date: | 2025-01-01 |
| Language: | English |
| ACCESSION: | WOS:001546957200001 |
| DOI: | 10.1038/s41591-025-03876-4 |
| PROVIDER: | wos |
| Notes: | Article; Early Access -- Source: Wos |
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