Elicio Therapeutics' ELI-002 7P Demonstrates Antigen Spreading in 87% of Phase 2 Patients
核心洞察
Elicio Therapeutics (搜索) reported that 87% (13/15) of evaluated Phase 2 patients treated with ELI-002 7P demonstrated antigen spreading to personalized tumor neoantigens beyond the targeted mKRAS (搜索) mutations.
The antigen spreading phenomenon expands immune responses from initial target antigens to new secondary tumor-specific antigens, potentially limiting tumor immune evasion and leading to more durable responses.
ELI-002 7P is an off-the-shelf immunotherapy targeting the seven most common KRAS (搜索) mutations present in 25% of all solid tumors (搜索), currently being studied in the Phase 2 AMPLIFY-7P trial for mKRAS (搜索)-driven pancreatic cancer (搜索).
Elicio Therapeutics (搜索) announced that its investigational cancer immunotherapy ELI-002 7P induced antigen spreading to personalized tumor neoantigens in 87% of evaluated patients from its ongoing Phase 2 AMPLIFY-7P trial. The findings demonstrate the therapy's ability to broaden immune responses beyond its primary mKRAS (搜索) targets, potentially enhancing anti-tumor immunity.
Antigen Spreading Results Show Broad Immune Activation
Among 90 evaluable patients treated with ELI-002 7P, 15 patients were selected for antigen spreading analyses based on availability of sufficient blood samples and tumor sequencing data. Using direct ex vivo Fluorospot and intracellular cytokine staining assays conducted on 5-12 tumor neoantigens per patient, researchers found that 87% (13/15) of evaluated patients demonstrated significant expansion of T cells specific for non-mKRAS (搜索) tumor neoantigens.
The antigen spreading responses were observed to additional common tumor driver mutations as well as personalized neoantigens. This phenomenon, also known as epitope spreading, refers to the expansion of immune response from initial target antigens to new secondary tumor-specific antigens that occurs during immunotherapy treatment as tumor cells are killed and release additional tumor antigens.
"We are extremely pleased to observe induction of personalized neoantigen-specific T cell responses in a significant majority of assessed Phase 2 patients," said Robert Connelly, Chief Executive Officer of Elicio. "These findings are consistent with our prior Phase 1 findings and further strengthen the robust immunogenicity and HLA data we have previously shared for our Phase 2 trial."
Consistent Pattern Across Clinical Development
The Phase 2 results align with previous observations from Phase 1 studies. In the Phase 1 AMPLIFY-201 trial with ELI-002 2P, 67% (6/9) of patients tested demonstrated antigen spreading with a median 3.4-fold change over baseline. The Phase 1 study of ELI-002 7P showed 70% (7/10) of patients with antigen spreading and a 2.7-fold median change. The current Phase 2 data shows an improved 87% response rate with a 10.6-fold median change over baseline.
Notably, 90% of Phase 2 patients showed responses to both CD4+ and CD8+ T cells, compared to 33.3% in the ELI-002 2P Phase 1 study and 50% in the ELI-002 7P Phase 1 study.
ELI-002 7P Targets Common KRAS Mutations
ELI-002 7P is designed to provide immune response coverage against seven of the most common KRAS (搜索) mutations present in 25% of all solid tumors (搜索). The therapy is built using Elicio's proprietary Amphiphile (AMP) technology, which delivers immunotherapeutics directly to lymph nodes by latching onto albumin protein at the injection site as it travels to lymphatic tissue.
The therapy consists of AMP-modified mutant KRAS (搜索) peptide antigens and ELI-004, an AMP-modified CpG oligodeoxynucleotide adjuvant, available as an off-the-shelf subcutaneous administration. This off-the-shelf approach offers potential benefits including low cost, rapid commercial scale manufacturing, and rapid availability to patients, particularly in neo-adjuvant settings and for prophylaxis in high-risk patients.
Clinical Development Program
ELI-002 is currently being studied in the ongoing Phase 1/2 AMPLIFY-7P trial (NCT05726864) in patients with mKRAS (搜索)-driven pancreatic cancer (搜索). The therapy has also been studied in patients with mKRAS-positive colorectal cancer (搜索) in Phase 1 studies. Updated AMPLIFY-201 Phase 1 data presented at the ESMO Immuno-Oncology Congress 2024 showed a 16.3-month median recurrence-free survival and 28.9-month median overall survival for the full study population.
Elicio plans to expand ELI-002 to other indications including mKRAS (搜索)-positive lung cancer (搜索) and other mKRAS-positive cancers. The company's pipeline also includes additional off-the-shelf therapeutic cancer immunotherapy candidates ELI-007 and ELI-008, targeting BRAF (搜索)-driven cancers and p53 hotspot mutations, respectively.
The broader multi-targeted immunity resulting from antigen spreading may limit tumors' potential to evade immune responses, potentially leading to more durable clinical responses and contributing to the prevention of relapse.