Elevation Oncology Reveals EO-3021 Combination Strategy for Gastric/Gastroesophageal Cancer

15 July 2024
Elevation Oncology, Inc., a prominent oncology company, announced plans to expand its current Phase 1 clinical trial by incorporating two new combination cohorts aimed at treating advanced gastric or gastroesophageal junction cancer. The company will evaluate EO-3021, an innovative antibody drug conjugate (ADC), in combination with ramucirumab and dostarlimab. Recently, Elevation Oncology signed clinical supply agreements with Eli Lilly and Company (Lilly) and GSK to facilitate these trials.

EO-3021 will be tested with ramucirumab, a VEGFR2 inhibitor, for second-line patients and with dostarlimab, a PD-1 inhibitor, for front-line settings. The initiation of dosing for these combination trials is expected by the end of 2024. Valerie Malyvanh Jansen, M.D., Ph.D., Chief Medical Officer of Elevation Oncology, emphasized the potential of EO-3021 to change the treatment landscape for tumors expressing Claudin 18.2, which is prevalent in many gastric and gastroesophageal junction adenocarcinomas. The company is eager to explore the benefits of combining EO-3021 with ramucirumab and dostarlimab, given the promising safety profile and efficacy seen in preclinical and clinical trials.

EO-3021 distinguishes itself as a potential best-in-class ADC targeting Claudin 18.2, designed with site-specific conjugation to enhance the stability of its linker-payload and minimize the release of free monomethyl auristatin E (MMAE). Preclinical studies and ongoing clinical trials have shown it to be well-tolerated with limited MMAE-related toxicities.

The initial development will explore two combination regimens for treating gastric or gastroesophageal junction cancer. The first regimen will combine EO-3021 with ramucirumab for second-line patients. Ramucirumab is currently approved for use with paclitaxel in treating patients who have progressed after prior chemotherapy. Elevation Oncology aims to introduce a combination that could offer improved safety and efficacy compared to the existing ramucirumab and paclitaxel duo.

The second regimen will combine EO-3021 with dostarlimab for front-line patients. Dostarlimab has approvals for use in certain types of endometrial cancer and accelerated approval for dMMR solid tumors. By combining it with EO-3021, Elevation Oncology seeks to create a treatment that provides better outcomes than current immunotherapy regimens for front-line gastric or gastroesophageal junction cancer patients.

Each cohort will undergo a dose escalation and expansion phase to assess safety and anti-tumor activity. Elevation Oncology will oversee and fund all clinical development activities, while Lilly and GSK will retain commercial rights to their respective compounds.

Elevation Oncology is also progressing with the monotherapy cohort of its Phase 1 trial for EO-3021, with plans to report initial safety and efficacy data by mid-third quarter 2024 and more comprehensive data in the first half of 2025.

EO-3021, also known as SYSA1801, is a clinical-stage ADC with potential best-in-class status. It targets Claudin 18.2, a protein typically found in gastric epithelial cells but exposed during malignant transformation. Elevation Oncology is assessing EO-3021 in patients with advanced, unresectable, or metastatic solid tumors likely to express Claudin 18.2, including gastric, gastroesophageal junction, pancreatic, or esophageal cancers.

Elevation Oncology retains exclusive rights to develop and commercialize EO-3021 outside Greater China and continues to push forward in the field of selective cancer therapies, leveraging their expertise in ADCs to address significant unmet medical needs across various solid tumors.

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