Study Explores the Potential of the ELI-002 Vaccine in Patients with KRAS-Driven Tumors

The ELI-002 vaccine, which targets lymph nodes in patients with KRAS-driven tumors, may be a potential treatment for those with KRAS-driven tumors who have minimal residual disease following tumor resection. A current phase 1/2 dose-escalation study is currently underway to test this hypothesis, according to a press release by Elicio Therapeutics.

ELI-002 is a novel and investigational amphiphile (AMP) therapeutic vaccine. The vaccine contains an AMP-modified mutant KRAS peptide antigens and ELI-004, which is an AMP-modified immune-stimulatory oligonucleotide adjuvant. This combination then targets lymph nodes where they may enhance action on important immune cells.

The vaccine utilizes the property amphiphile (AMP) platform that is meant to deliver investigational immunotherapeutics directly to the lymph nodes. Research suggests that this specific delivery site may help to activate, educate, and amply immune cells, leading to a persistence response. Preclinical models have found that by engaging the lymph nodes, an increase immune response is produced.

The AMPLIFY-201 (NCT04853017) study is a randomized, parallel assignment study that will follow a 3 + 3 design. The planned competition date of the study is March 2025. The study has a planned enrollment of 159 participants. The primary end point of phase 1A is maximum-tolerated dose of the agent which will be evaluated in 18 patients. The primary end point of phase 1B is safety up to 30 days after last dose. The primary end point of phase 2 is to determine if ELI-002 improves relapse-free survival (RFS) compared with observation alone.

The secondary end point of phase 1 is to determine the circulating tumor (ct)DNA clearance rate up to 6 months. Secondary end points explored in the phase 2 portion of the include the safety of the vaccine, the ctDNA clearance, 1-year RFS, overall survival (OS) up to 24 months, and the objective response rate (ORR). 

The study is composed of 3 phases. In phase 1a, a 3+3 dose-escalation design was used. Eighteen patients were treated in 3 planned dose level cohorts. During phase 1b, the 3 dose expansion cohorts, totaling up to 17 subjects in each cohort were evaluated for preliminary anti-tumor activity. In phase 2, patients will be randomized to either observation or immunization.

In the experimental phase 1a arm, patients received an ELI-002 injection once a week for 4 weeks followed by bi-weekly injections for 4 weeks during the immunization period. During the booster period, 4 more doses were administered over 4 weeks. During the experimental 1b phase, patients followed the same schedule at the recommended phase 1A dose schedule. During phase 2, patients will follow the same schedule, however, they will be randomized to either receive the vaccine or observation.

In order to participate, patients must be 18 years old or older, have a KRAS/NRAS mutated G12D or G12R solid tumor, have positive circulating tumor DNA despite prior standard therapy including surgery and chemoradiotherapy where applicable, be negative for recurrent disease, and have an ECOG performance status of 0 or 1. Patients with tumor mutations with a specific approved therapy, known brain metastases, or uses immunosuppressive drugs are not eligible to participate.

“RAS mutations, particularly KRAS mutations, are found in approximately 25% of tumors and have been considered difficult to target due to the number of mutations that can cause disease. In this study, our lymph node-targeted therapeutic vaccine ELI-002 is designed to target all seven common KRAS mutations, including G12C,” said Christopher Haqq, MD, PhD, Elicio’s executive vice president, head of research and development, and chief medical officer in a press release. “We believe that the ability of our proprietary AMP platform to deliver ELI-002 directly to the lymph nodes, the control center of the immune system, may stimulate an enhanced immune response.”

The study is currently recruiting patients in California, Iowa, Massachusetts, Michigan, Missouri, New York, Tennessee, and Texas.

_REFERENCE:

_{Elicio Therapeutics announces initiation of its phase 1/2 dose-escalation study of ELI-002 (AMPLIFY-201) in KRAS-driven cancers. News release. Elicio Therapeutics. June 29, 2021. Accessed July 7, 2021. https://bit.ly/3ABi0Hk.}