FDA Supports Registrational Strategy for ELI-002 in KRAS-Driven Cancers

• The FDA has provided supportive feedback in an end of phase 1 type B meeting about the registrational strategy for ELI-002.
• Based on the feedback from the FDA, the company anticipates submitting a biologics license application (BLA) contingent upon the results of a planned phase 3 trial.
• ELI-002 is an investigational therapeutic cancer vaccine which aims to treat cancers that are driven by the common KRAS mutations.

Following a type B end of phase 1 meeting with the FDA, Elicio Therapeutics has received positive feedback regarding the registrational strategy for ELI-002. If the planned phase 3 trial is successful, the company expects to file a BLA.¹

The FDA provided feedback on key elements of the potential phase 3 trial of ELI-002, including its study design, dose, schedule, patient population, and primary end point analysis.

“The feedback received from the FDA supports our proposed phase 3 study design, is strongly aligned with our therapeutic approach and is another step forward in our effort to bring this cancer immunotherapy forward to patients,” said Christopher Haqq, MD, PhD, executive vice president, head of research and development and chief medical officer of Elicio, in a press release. “In a recent type B meeting, we obtained alignment with the FDA on the principal elements of the phase 3 study design, including the dose, dosing schedule, target patient population (KRAS-mutated pancreatic adenocarcinoma) and the primary study end point of disease-free survival, based on modified RECIST criteria.”

ELI-002 is an investigational AMP cancer vaccine that targets cancers driven by mutations in the KRAS gene. The vaccine combines 2 components: AMP-modified mutant KRAS peptide antigens and ELI-004, an AMP-modified CpG oligodeoxynucleotide adjuvant, which can be administered subcutaneously.¹

The 2-peptide formulation of ELI-002 (ELI-002 2P) has been tested in the phase 1 AMPLIFY-201 trial (NCT04853017) for patients with high-risk, KRAS-driven solid tumors after surgery and chemotherapy. The 7-peptide formulation (ELI-002 7P) is currently being studied in the phase 1/2 AMPLIFY-7P trial (NCT04853017) for patients with KRAS-driven pancreatic cancer. This formulation, ELI-002 7P, targets 7 of the most common KRAS mutations, including G12D, G12R, G12V, G12A, G12C, G12S, and G13D. According to an interview with Haqq, these mutations are present in 25% of all solid tumor cancers as well as 88% of patients with pancreatic ductal adenocarcinoma.

“Approximately 90% of pancreatic cancers are positive for KRAS mutations and in most cases, patients with circulating tumor DNA post-surgery relapse. There are no treatment options during this “wait and see” observation window before relapse,” Haqq explained.

The phase 1/2 AMPLIFY-7- trial is evaluating the safety and efficacy of ELI-002 7P as adjuvant treatment in patients with solid tumors with KRAS/NRAS mutations.² ​​The study had 3 phases.

In phase 1A, Amph-Peptides 7P was combined with the recommended phase 2 dose of Amph-CpG-7909 (10 mg) and tested at 2 dose levels of 1.4 mg and 4.9 mg, with 6 patients per dose level. Phase 1B included a dose-expansion cohort of up to 17 patients with colorectal cancer. ELI-002 7P will be administered subcutaneously (SC) weekly for 4 weeks, followed by bi-weekly injections during the immunization period and additional injections during the booster period. Finally, phase 2 enrolled 135 patients with PDAC who were randomly assigned in a 2:1 ratio to receive ELI-002 7P or observation. Patients receiving ELI-002 7P were given weekly SC injections during the immunization and booster periods.

Patients with KRAS- or NRAS-mutated disease, an ECOG performance status of 0 or 1, and a screening CT that is negative for recurrent disease were eligible for enrollment in the study. In phase 1 of the trial, patients must also be positive for circulating tumor DNA and/or elevated serum tumor biomarkers. Patients who have a presence of tumor mutations where specific therapy is approved, known brain metastases, or those who use immunosuppressive drugs will be excluded from the study.

The primary end point of the study is safety and secondary end points include determining the proportion of patients with biomarker reduction, biomarker clearance, biomarker reduction by biomarker type, and biomarker clearance by biomarker type.

The phase 2 randomized study of ELI-002 has been fully enrolled, with an interim analysis of disease-free survival expected in the first half of 2025.¹ Positive results from this analysis could support advancing the treatment into phase 3 development.

“We believe that ELI-002 could have a transformational role in the management of difficult-to-treat mKRAS cancers as an off-the-shelf monotherapy treatment for patients who completed neoadjuvant, perioperative or adjuvant chemotherapy and yet remain at elevated risk of disease recurrence,” said Robert Connelly, chief executive officer of Elicio, in the press release. “The continued development of ELI-002 is supported by encouraging clinical results that have demonstrated a favorable safety profile, a strong correlation between T-cell response, tumor biomarker reductions and reduced risk of recurrence or death.”

REFERENCES:

1. Elicio Therapeutics reaches alignment with FDA on ELI-002 registrational strategy. News release. Elicio Therapeutics, Inc. January 22, 2025. Accessed January 22, 2025. https://tinyurl.com/4rssr8x6

2. A study of ELI-002 in subjects with KRAS mutated pancreatic ductal adenocarcinoma (PDAC) and other solid tumors (AMPLIFY-201). ClinicalTrials.gov. Updated January 17, 2025. Accessed January 22, 2025. https://clinicaltrials.gov/study/NCT04853017