Elevation Oncology has announced promising initial data from its Phase 1 clinical trial evaluating EO-3021 in patients with advanced, unresectable, or metastatic solid tumors likely to express Claudin 18.2. The data, which focuses on gastric and gastroesophageal junction (GEJ) cancers, reveals encouraging efficacy and a differentiated safety profile for the antibody-drug conjugate (ADC). The study suggests EO-3021 could offer a new treatment option for a subset of patients with these aggressive cancers.
Initial Efficacy Data
As of the data cutoff date of June 10, 2024, efficacy data was available for 15 patients with gastric or GEJ cancers. A key finding was that 7 of these patients (47%) had tumors expressing Claudin 18.2 in ≥20% of tumor cells, as determined by immunohistochemistry (IHC). In this Claudin 18.2-enriched group, the objective response rate (ORR) was 42.8%, with three confirmed partial responses. The disease control rate (DCR) in this group reached 71.4%, including two patients with stable disease.
In contrast, among the 8 patients with Claudin 18.2 expression <20%, the ORR was 0%, and the DCR was 50%, with four patients experiencing stable disease. These results underscore the importance of Claudin 18.2 expression as a potential predictive biomarker for EO-3021 response.
Safety and Tolerability
EO-3021 demonstrated a favorable safety profile in the Phase 1 trial. Among the 32 patients treated in the dose escalation phase, no Grade 4 or 5 treatment-related adverse events were reported. Less than 10% of patients discontinued treatment due to adverse events. Notably, there were no reported cases of neutropenia or peripheral neuropathy/hypoesthesia, which are known toxicities associated with monomethyl auristatin E (MMAE), the cytotoxic payload of EO-3021.
The most common treatment-emergent adverse events (reported in ≥20% of patients) included nausea (56%), decreased appetite (47%), fatigue (41%), and diarrhea (28%). Four dose-limiting toxicities (DLTs) were observed at the 2.9 mg/kg dose level, leading to the selection of 2.0 mg/kg and 2.5 mg/kg Q3W doses for further evaluation in the dose expansion portion of the trial.
Clinical Development Plans
Elevation Oncology is moving forward with the clinical development of EO-3021. The company plans to initiate enrollment in the dose expansion portion of the Phase 1 trial, further exploring the 2.0 mg/kg and 2.5 mg/kg doses. The primary objective is to evaluate the safety, tolerability, and preliminary anti-tumor activity of EO-3021 in patients with gastric or GEJ cancer who have progressed on or after standard therapy or are intolerant to available standard therapies.
Furthermore, Elevation Oncology intends to expand the Phase 1 trial to include combination cohorts, evaluating EO-3021 in combination with ramucirumab (a VEGFR2 inhibitor) in the second-line setting and with dostarlimab (a PD-1 inhibitor) in the first-line setting. Dosing in the combination portion of the trial is expected to begin by year-end 2024. Additional data from the dose expansion cohort is anticipated in the first half of 2025.
Expert Commentary
"Gastric and GEJ cancers are devastating diseases, which occur frequently in the U.S. and globally and which, despite recent advancements, still have high levels of mortality," said Kohei Shitara, M.D., Chief, Department of Gastrointestinal Oncology, National Cancer Center Hospital East in Kashiwa, Japan, and principal investigator on the Phase 1 clinical trial. "There is a particular need for highly selective therapies that benefit patients with Claudin 18.2-expressing tumors. To that end, I am excited by the initial data with EO-3021, which suggest it could change the treatment paradigm for a significant portion of patients with gastric or GEJ cancer."
About EO-3021
EO-3021 is a differentiated, clinical-stage antibody-drug conjugate (ADC) comprised of an IgG1 monoclonal antibody targeting Claudin 18.2. It is site-specifically conjugated to MMAE via a cleavable linker, with a drug-to-antibody ratio (DAR) of 2. Elevation Oncology holds exclusive rights to develop and commercialize EO-3021 in all global territories outside Greater China.
