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

Autor: Pant S; The University of Texas MD Anderson Cancer Center, Houston, TX, USA. spant@mdanderson.org., Wainberg ZA; University of California, Los Angeles, Los Angeles, CA, USA., Weekes CD; Massachusetts General Hospital, Boston, MA, USA., Furqan M; University of Iowa, Iowa City, IA, USA., Kasi PM; University of Iowa, Iowa City, IA, USA., Devoe CE; Northwell Health, Lake Success, NY, USA., Leal AD; University of Colorado School of Medicine, Aurora, CO, USA., Chung V; City of Hope, Duarte, CA, USA., Basturk O; Memorial Sloan Kettering Cancer Center, New York, NY, USA., VanWyk H; Elicio Therapeutics, Boston, MA, USA., Tavares AM; Elicio Therapeutics, Boston, MA, USA., Seenappa LM; Elicio Therapeutics, Boston, MA, USA., Perry JR; Elicio Therapeutics, Boston, MA, USA., Kheoh T; Elicio Therapeutics, Boston, MA, USA., McNeil LK; Elicio Therapeutics, Boston, MA, USA., Welkowsky E; Elicio Therapeutics, Boston, MA, USA., DeMuth PC; Elicio Therapeutics, Boston, MA, USA., Haqq CM; Elicio Therapeutics, Boston, MA, USA. chris.haqq@elicio.com., O'Reilly EM; Memorial Sloan Kettering Cancer Center, New York, NY, USA. oreillye@mskcc.org.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2024 Feb; Vol. 30 (2), pp. 531-542. Date of Electronic Publication: 2024 Jan 09.
DOI: 10.1038/s41591-023-02760-3
Abstrakt: 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 .
(© 2024. The Author(s).)
Databáze: MEDLINE
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