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Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial

2024; Nature Portfolio; Volume: 30; Issue: 2 Linguagem: Inglês

10.1038/s41591-023-02760-3

1546-170X

Shubham Pant, Zev A. Wainberg, Colin D. Weekes, Muhammad Furqan, Pashtoon Murtaza Kasi, Craig Devoe, Alexis D. Leal, Vincent Chung, Olca Baştürk, Haley VanWyk, Amy Tavares, Lochana M. Seenappa, James Perry, Thian Kheoh, Lisa K. McNeil, Esther Welkowsky, Peter C. DeMuth, Christopher M. Haqq, Eileen M. O’Reilly,

RNA Interference and Gene Delivery

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