On June 27, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported plans to expand its ongoing Phase 1 clinical trial to include two combination cohorts evaluating EO-3021 for the treatment of advanced gastric or gastroesophageal junction cancer (Press release, Elevation Oncology, JUN 27, 2024, View Source [SID1234644584]). Following recently signed clinical supply agreements with Eli Lilly and Company (Lilly) and GSK, respectively, Elevation Oncology will evaluate EO-3021 in combination with ramucirumab, a VEGFR2 inhibitor, in second-line patients and in combination with dostarlimab, a PD-1 inhibitor, in the front-line setting. The Company expects to initiate dosing in the combination portion of the Phase 1 trial by year-end 2024.

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"EO-3021 has the potential to change the treatment paradigm for tumors that express Claudin 18.2, including a majority of gastric and gastroesophageal junction adenocarcinomas," said Valerie Malyvanh Jansen, M.D., Ph.D., Chief Medical Officer of Elevation Oncology. "Based on safety data from preclinical and clinical trials, we believe EO-3021 benefits from a differentiated safety profile and will be readily combinable. We also know that combination-based regimens are a mainstay of cancer care, and that the combination of two therapies with distinct mechanisms of action often enables patients to achieve deeper, more durable responses. As such, we are excited to begin evaluating EO-3021 together with ramucirumab, a VEGFR2 inhibitor, and with dostarlimab, a PD-1 inhibitor, in the second- and first-line settings, respectively. In parallel, we continue to advance our Phase 1 trial of EO-3021 monotherapy toward initial safety and efficacy data by mid-third quarter."

Clinical Development Plans for EO-3021 in Combination

EO-3021 is a differentiated, potential best-in-class antibody drug conjugate (ADC) targeting Claudin 18.2. EO-3021 was designed with site-specific conjugation at glutamine (Q295), with the goal of increasing the stability of the linker-payload and minimizing the potential for free monomethyl auristatin E (MMAE) compared to traditional cysteine-based conjugation. In preclinical studies and the Phase 1 clinical trial conducted by Elevation Oncology’s partner, data showed a favorable tolerability profile, with limited MMAE-related toxicities.

Initial development of EO-3021 in combination will explore two regimens for the treatment of gastric or gastroesophageal junction cancer:

EO-3021 in combination with ramucirumab in second-line patients: Ramucirumab is a monoclonal antibody that targets VEGFR2 and is approved for use in combination with paclitaxel for the treatment of second-line gastric or gastroesophageal junction cancer with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. With EO-3021, Elevation Oncology aims to introduce a combination agent that, when paired with ramucirumab, can potentially deliver improved safety and efficacy as compared to the approved combination of ramucirumab and paclitaxel.
EO-3021 in combination with dostarlimab in front-line patients: Dostarlimab is approved alone and in combination with chemotherapy for certain types of dMMR and MSI-H endometrial cancer in the US; it also has an accelerated approval in certain dMMR solid tumors. By combining EO-3021 and an immune checkpoint inhibitor, Elevation Oncology aims to deliver synergistic benefit, potentially offering patients improved outcomes beyond those seen with existing immunotherapy regimens for gastric or gastroesophageal junction cancer in the front-line setting.
Each combination cohort will include a dose escalation and expansion portion, evaluating the combination of EO-3021 and ramucirumab or EO-3021 and dostarlimab. The primary endpoints will include safety and anti-tumor activity. Elevation Oncology plans to initiate dosing in the combination portion of the Phase 1 trial by year-end 2024.

In June 2024, Elevation Oncology entered into clinical supply agreements with Lilly and GSK to supply their respective compounds for these combination cohorts. Elevation Oncology will sponsor and conduct all clinical development of both combinations and will assume all costs associated with the study. All companies will retain commercial rights to their respective compounds.

Elevation Oncology continues to enroll patients in the monotherapy cohort of its ongoing Phase 1 clinical trial (NCT05980416) and remains on track to share initial safety and efficacy data by mid-third quarter 2024, with additional data in the first half of 2025.

About EO-3021

EO-3021 (also known as SYSA1801) is a differentiated, clinical-stage antibody drug conjugate (ADC) with best-in-class potential comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2. EO-3021 is site-specifically conjugated to the monomethyl auristatin E (MMAE) payload via a cleavable linker with a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformation, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in a Phase 1 study (NCT05980416) 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 has the exclusive rights to develop and commercialize EO-3021 in all global territories outside Greater China.