On December 11, 2024 Enterome, a clinical-stage company developing first-in-class immunomodulatory drugs for cancer based on its unique Mimicry platform, reported that initial clinical data from the ongoing Phase 1/2 ‘AUDREY’ trial evaluating its innovative OncoMimics immunotherapy EO4010 in microsatellite stable metastatic colorectal cancer (CRC), will be presented at the ESMO (Free ESMO Whitepaper) Immuno-Oncology (IO) Congress, taking place in Geneva, Switzerland, December 11-13, 2024 (Press release, Enterome, DEC 11, 2024, View Source [SID1234649043]).
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The AUDREY trial (EOCRC2-22) assesses the safety, tolerability, and preliminary efficacy of EO4010, in combination with nivolumab +/- bevacizumab, in patients with microsatellite stable (MSS), unresectable, and previously treated metastatic colorectal cancer (mCRC) — an indication with limited effective treatment options and poor clinical outcomes. EO4010 includes five OncoMimics peptides that mimic tumor-associated antigens (TAAs) highly expressed in colorectal cancer, designed to stimulate CD8+ T cells to target and eliminate tumor cells.
Poster presentation details:
Abstract #457
Title: EO4010 (EO) + nivolumab (N) ± bevacizumab (B) in patients (pts) with microsatellite stable (MSS) metastatic colorectal carcinoma (mCRC)
Presenting Author: Romain Cohen, Department of medical oncology, Saint-Antoine hospital, AP-HP, and Assistant Professor of Oncology at Sorbonne University, Paris
Poster Session: presentation time December 12, 12:00 PM-13:00 PM CET
Key findings:
Among the 17 patients evaluated in Cohort 2 of the AUDREY trial, one achieved a partial response, showing a 46% reduction in liver metastases, a 34% reduction in lung metastases, and normalization of carcinoembryonic antigen (CEA) levels. Two additional patients achieved stable disease; one demonstrated a 7% reduction in lung metastases and a marked reduction of tumor biomarkers CEA/CA19-9, while another maintained stable disease beyond 17 weeks. Six patients showed stable disease in target lesions, though with progression in non-target lesions, along with some biomarker reductions.
In Cohort 3, which included bevacizumab in addition to EO4010 and nivolumab, three out of five evaluated patients achieved stable disease, with one continuing treatment > 24 weeks (lung met’s +8%, CEA normalized).
Immune response analysis showed EO4010-specific CD8+ T cells in 12 out of 13 tested patients, with cross-reactivity to the targeted tumor antigens. Notably, over 80% of these cells were effector memory T cells after five weeks, demonstrating a sustained, targeted immune response.
Dr. Romain Cohen, Coordinating Investigator for the AUDREY trial, commented, "These early data highlight EO4010’s potential to induce targeted immune responses and shrinkage of liver metastases in patients with pretreated microsatellite stable metastatic colorectal cancer. We look forward to continued follow-up and further results from the AUDREY trial."
Pierre Bélichard, Chief Executive Officer of Enterome, added, "The presentation of EO4010 data at ESMO (Free ESMO Whitepaper) IO reflects our dedication to pioneering next-generation immunotherapies for cancers with high unmet needs. These findings support the potential of our OncoMimics platform to deliver new options for patients, leveraging multi-target engagement to address tumor heterogeneity and prevent immune escape."
About OncoMimics
OncoMimics immunotherapies are designed to activate pre-existing effector memory T cells against bacterial (non-self) peptides that strongly cross-react with corresponding Tumor-Associated Antigens (TAAs), or B cell markers expressed on tumoral cells, resulting in a rapid, targeted cytotoxic response against cancer cells.
About EO4010
EO4010, Enterome’s third clinical-stage OncoMimics candidate, combines five microbial-derived peptides that mimic HLA-A2 restricted CD8+ T cell epitopes from five TAAs: BIRC5/survivin, FOXM1, UBE2C (UBCH10), CDC20, and KIF2C (MCAK). It also includes a CD4 helper peptide, Universal Cancer Peptide 2 (UCP2), to bolster immune activation. The BIRC5 and FOXM1 mimic peptides, also used in EO2401, have shown strong immune responses and correlated clinical outcomes in combination with nivolumab +/- bevacizumab for glioblastoma.
About AUDREY
AUDREY (EOCRC2-22/NCT05589597) is a multicenter, open-label Phase 1/2 trial investigating EO4010 in monotherapy and in combination with nivolumab for treatment of patients with unresectable, previously treated, metastatic colorectal cancer. The trial is assessing safety, tolerability, immunogenicity and preliminary efficacy in 42 patients at centers in Europe and the US.
About colorectal cancer
Colorectal cancer (CRC) is the third most common cancer in men and the second in women, contributing to 10% of all cancers worldwide. It is the fourth most common cause of cancer-related death, with more than 600,000 deaths annually. Despite all efforts regarding surgery and adjuvant therapy, 25% of patients with localized CRC later develop metastases, and around 20% of cases are metastatic at diagnosis. Thus, CRC continues to be a major therapeutic challenge with a considerable number of patients experiencing premature death, fewer than 20% of those diagnosed with recurring/metastatic disease surviving beyond 5 years from diagnosis.