Journal article
Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial
Nature medicine, Vol.30(2), pp.531-542
02/2024
DOI: 10.1038/s41591-023-02760-3
PMCID: PMC10878978
PMID: 38195752
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 .
Details
- Title: Subtitle
- Lymph-node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: the phase 1 AMPLIFY-201 trial
- Creators
- Shubham Pant - The University of Texas MD Anderson Cancer CenterZev A Wainberg - University of California, Los AngelesColin D Weekes - Massachusetts General HospitalMuhammad Furqan - University of IowaPashtoon M Kasi - University of Iowa, Iowa City, IA, USACraig E Devoe - Northwell HealthAlexis D Leal - University of Colorado HealthVincent Chung - City Of Hope National Medical CenterOlca Basturk - Memorial Sloan Kettering Cancer CenterHaley VanWyk - Elicio Therapeutics, Boston, MA, USAAmy M Tavares - Elicio Therapeutics, Boston, MA, USALochana M Seenappa - Elicio Therapeutics, Boston, MA, USAJames 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.comEileen M O'Reilly - Memorial Sloan Kettering Cancer Center
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.30(2), pp.531-542
- DOI
- 10.1038/s41591-023-02760-3
- PMID
- 38195752
- PMCID
- PMC10878978
- NLM abbreviation
- Nat Med
- ISSN
- 1078-8956
- eISSN
- 1546-170X
- Grant note
- name: Elicio Therapeutics
- Language
- English
- Electronic publication date
- 01/09/2024
- Date published
- 02/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984543458802771
Metrics
4 Record Views