Development of EO-3021 Discontinued for Gastric and GEJ Cancers

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Elevation Oncology discontinues EO-3021 for gastric and gastroesophageal junction cancers after phase 1 trial shows insufficient efficacy.

Elevation Oncology discontinues EO-3021 for gastric and GEJ cancers after phase 1 trial shows insufficient efficacy, focusing on advancing EO-1022 instead.

Elevation Oncology announced that it has elected to discontinue development of EO-3021, an antibody-drug conjugate (ADC), which was being developed for the treatment of advanced, unresectable or metastatic gastric and gastroesophageal junction (GEJ) cancers, according to a news release from the company.

"We are turning our focus to our potentially differentiated HER3 ADC, EO-1022, which incorporates glycan site-specific conjugation and is designed to address significant and emerging unmet needs in many HER3-expressing cancers,” said Joseph Ferra, president and CEO of Elevation Oncology, in the release. “We look forward to presenting preclinical data supporting its potential at the AACR Annual Meeting next month."

This decision to discontinue clinical development of the drug was based on study data from the dose escalation and expansion stages of a phase 1 trial.

Data from the trial showed that treatment with EO-3021 as a monotherapy had an objective response rate pf 22.2% and a disease control rate of 72.2%. The trial evaluated 36 patients with gastric or GEJ cancer, of which at least 20% of tumor cells expressed Claudin 18.2, a tight junction protein, with moderate to strong staining intensity (IHC 2+/3+) as determined by immunohistochemistry.

Glossary:

Objective response rate: the percentage of patients with tumor shrinkage or complete remission based on clinical criteria.

Disease control rate: the percentage of patients with stable disease, partial response or complete response.

In a safety analysis of all enrolled patients (85 patients), EO-3021 was generally well tolerated, with side effects consistent with previous data, including minimal hematological toxicity and hepatotoxicity, and no peripheral neuropathy, which is nerve damage outside the brain and spinal cord, or hypoesthesia, which describes a decreased or reduced sensitivity to sensory stimuli.

Elevation Oncology plans to continue development of the HER3 ADC EO-1022, which uses a monomethyl auristatin E (MMAE) payload, a potent cytotoxic agent used as payload for ADCs, and glycan site-specific conjugation, which attaches a drug to a specific sugar chain or an antibody. EO-1022 is being developed for the treatment of patients living with solid tumors that express the gene mutation HER3.

Preclinical data will be presented at the American Association for Cancer Research Annual Meeting 2025, with an investigational new drug application planned for 2026.

An investigational new drug application is a request submitted to the Food and Drug Administration (FDA) to conduct clinical trials with a new drug or biological product that has not yet been approved for marketing, as per the FDA’s website.

In the phase 1, open-label, multi-center trial, eligible patients had cancer that progressed after standard treatment or could not tolerate available therapies. EO-3021 was administered intravenously, meaning through the vein, every three weeks. Tumor samples were required for enrollment, and CLDN 18.2 expression was assessed retrospectively. Enrollment began in August 2023.

"We are deeply disappointed by these results from our phase 1 trial,” Ferra continued in the release. “Despite continuing to demonstrate differentiated safety as a more combinable ADC, updated efficacy data suggest that treatment with EO-3021 does not meet our bar for success and is insufficient to provide patients a competitive benefit-risk profile compared to other Claudin 18.2 ADCs in development. Based on these data, we have decided to discontinue further development of EO-3021. I want to express my tremendous gratitude to the patients, physicians and site coordinators who participated in the EO-3021 clinical trial."

According to the National Cancer Institute’s website, ADCs are targeted therapies that combine a monoclonal antibody, which binds to specific proteins on cancer cells, with a potent chemotherapy drug via a chemical linker, delivering the drug directly to cancer cells and minimizing harm to healthy cells.

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