Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: The phase 1 AMPLIFY-201 trial Journal Article
| Authors: | Pant, S.; Wainberg, Z. A.; Weekes, C. D.; Furqan, M.; Kasi, P. M.; Devoe, C. E.; Leal, A. D.; Chung, V.; Basturk, O.; VanWyk, H.; Tavares, A. M.; Seenappa, L. M.; Perry, J. R.; Kheoh, T.; McNeil, L. K.; Welkowsky, E.; DeMuth, P. C.; Haqq, C. M.; O’Reilly, E. M. |
| Article Title: | Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: The phase 1 AMPLIFY-201 trial |
| Abstract: | Pancreatic and colorectal cancers are often KRAS mutated and are incurable when tumor DNA or protein persists or recurs after curative intent therapy. Cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909). We treated 25 patients (20 pancreatic and five colorectal) who were positive for minimal residual mKRAS disease (ctDNA and/or serum tumor antigen) after locoregional treatment in a phase 1 study of fixed-dose Amph-Peptides-2P and ascending-dose Amph-CpG-7909; study enrollment is complete with patient follow-up ongoing. Primary endpoints included safety and recommended phase 2 dose (RP2D). The secondary endpoint was tumor biomarker response (longitudinal ctDNA or tumor antigen), with exploratory endpoints including immunogenicity and relapse-free survival (RFS). No dose-limiting toxicities were observed, and the RP2D was 10.0 mg of Amph-CpG-7909. Direct ex vivo mKRAS-specific T cell responses were observed in 21 of 25 patients (84%; 59% both CD4+ and CD8+); tumor biomarker responses were observed in 21 of 25 patients (84%); biomarker clearance was observed in six of 25 patients (24%; three pancreatic and three colorectal); and the median RFS was 16.33 months. Efficacy correlated with T cell responses above or below the median fold increase over baseline (12.75-fold): median tumor biomarker reduction was −76.0% versus −10.2% (P < 0.0014), and the median RFS was not reached versus 4.01 months (hazard ratio = 0.14; P = 0.0167). ELI-002 2P was safe and induced considerable T cell responses in patients with immunotherapy-recalcitrant KRAS-mutated tumors. ClinicalTrials.gov identifier: NCT04853017. © The Author(s) 2024. |
| Keywords: | genetics; clinical trial; neoplasm recurrence, local; pathology; peptide; tumor antigen; tumor marker; colorectal neoplasms; antigens, neoplasm; colorectal tumor; tumor recurrence; peptides; phase 1 clinical trial; protein p21; proto-oncogene proteins p21(ras); vaccine; vaccines; humans; human; biomarkers, tumor |
| Journal Title: | Nature Medicine |
| Volume: | 30 |
| Issue: | 2 |
| ISSN: | 1078-8956 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-02-01 |
| Start Page: | 531 |
| End Page: | 542 |
| Language: | English |
| DOI: | 10.1038/s41591-023-02760-3 |
| PUBMED: | 38195752 |
| PROVIDER: | scopus |
| PMCID: | PMC10878978 |
| DOI/URL: | |
| Notes: | Article -- MSK corresponding author is Eileen O'Reilly -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work