ELI-002 is a structurally novel AMP therapeutic vaccine targeting KRAS-driven cancers. KRAS mutations are among the most prevalent in human cancers. ELI-002 is comprised of AMP-modified mutant KRAS peptide antigens and ELI-004, an AMP-modified immune-stimulatory oligonucleotide adjuvant.
The AMPLIFY-201 trial is being conducted at multiple sites, including US cancer treatment institutions such as MD Anderson, Memorial Sloan Kettering, Sarah Cannon Research Institute, Washington University St. Louis, and Henry Ford Health System. Following an initial dose escalation phase, Elicio Therapeutics expanded patient eligibility to evaluate the potential of ELI-002 as a treatment for a number of KRAS-mutated cancers. AMPLIFY-201 is strategically constructed to target patients with minimal residual disease, or MRD, a stage where tumor burden and immunosuppressive effects within the tumor are lower.
Data from adult patients with high-relapse risk with KRAS G12D- or G12R-mutated pancreatic and colorectal cancer treated with ELI-002 2P in the AMPLIFY-201 study a first-in-human safety and efficacy trial of adjuvant ELI-002 2P immunotherapy (NCT04853017) were presented in a poster discussion session at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. The study’s aim was to assess safety, immunogenicity, and antitumor activity using a novel adjuvant trial design in patients with minimal residual disease (MRD) following standard locoregional treatment.
In the AMPLIFY-201 trial no dose-limiting toxicities, treatment-related SAEs, or cytokine release syndrome were observed, and no maximum tolerated dose was identified. All adverse events were Grade 1 and Grade 2, fatigue (16%), headache (16%), and injection site reaction (12%).
In terms of tumor ctDNA/Serum tumor antigen response, ELI-002 2P monotherapy showed good pharmacologic activity in high relapse-risk PDAC and CRC with 17/22 (77.3%) biomarker reduction and 7/22 (31.8%) biomarker clearance (4PDAC, 3 CRC).
Also, responses occurred for both G12D and G12R and among the patients with and without known Class I mKRAS-restricting HLAs, suggesting potential for broad utility among mKRAS-driven solid cancer patients.
Overall 87% of patients generated expanded mKRAS –specific T-cell responses following ELI-002 2P immunization, with 100% responders at the highest doses. The CD4 and CD8 T-cell responses were observed with 50% generating mixed CD4 and CD8 responses.
KOL insights
“mKRAS-specific T cells have been shown to mediate anti-tumor efficacy, which prompted us to assess ELI-002 in high relapse-risk patients where tumor biomarkers can provide an early efficacy signal.” –Expert Opinion.
“We are encouraged by the findings which showed that ELI-002 was well-tolerated. The trial enabled patients to enroll with minimal disease which reduces the chances of an immunosuppressive tumor environment and increases the ratio of T cells to target tumor cells.” –Expert Opinion.
Conclusion
The Lymph node-targeted therapeutic mKRAS-specific Cancer Vaccine ELI-002 was found to be safe and well-tolerated with no dose-limiting toxicity and no CRS. RPZD determined at 10 mg Amph-CpG-7909: Favorable safety, tumor biomarker response, and T cell response. A novel adjuvant trial design using ctDNA / serum tumor biomarkers was feasible with the goal to minimize HLA loss, tumor-acquired immunosuppressive mechanisms, and Maximize T-cell and tumor-cell ratio. Tumor biomarker data (ctDNA and serum tumor antigen) can provide early efficacy signals. A high proportion of ELI-002 2P patients had tumor biomarker reduction (77%), and a subset achieved clearance (32%) with notable mKRAS-specific T cell responses induced, average 56-fold (2–423) increase directly ex vivo T-cell infiltration was 10–29-fold higher than literature in pancreatic tumors.
A new formulation, ELI-002 7P, is currently being studied in AMPLIFY-7P, a Phase I/II trial in patients with high relapse risk mKRAS-driven solid tumors. ELI-002 7P covers seven common KRAS mutations, expanding patient reach and potentially overcoming bypass resistance mechanisms. Elicio therapeutics with its focus on revolutionizing treatment options and offering hope to a broader patient population, the ELI-002 7P study stands as a testament to the relentless pursuit of innovation in the field of cancer research. If successful, it has the potential to reshape the future of mKRAS-driven solid tumor therapy, bringing us closer to the day when these formidable diseases can be conquered
