NEW YORK – Elevation Oncology last week said it will discontinue development of its claudin (CLDN) 18.2-targeted antibody-drug conjugate (ADC) EO-3021 in gastric cancer based on disappointing results from a Phase I trial.
In conjunction with the program's termination, Elevation will reduce its workforce by about 70 percent in order to extend its cash runway into the second half of 2026. As part of this reduction, Elevation Chief Medical Officer Valerie Malyvanh Jansen will be stepping down at the end of the month. As of Dec. 31, 2024, the company had 34 full-time employees.
In January, Elevation narrowed the Phase I trial of EO-3021 to focus only on patients who have CLDN 18.2-expressing gastric or gastroesophageal cancers. The investigators initially enrolled all-comers with advanced or metastatic cancers likely to express CLDN18.2, such as gastric, pancreatic, or esophageal tumors, and tested patients' tumors for CLDN18.2 expression during the trial. Based on data suggesting that patients with CLDN18.2-expressing tumors were more likely to respond to EO-3021, Elevation amended the trial design so that patients were required to have a certain level of CLDN18.2 expression in their tumors to enroll in the study.
At that time, the Boston-based firm also added a combination treatment arm in that same Phase I trial, in which patients would receive EO-3021 with either GlaxoSmithKline's PD-1 inhibitor Jemperli (dostarlimab) in the frontline setting or Eli Lily's VEGFR2 inhibitor Cyramza (ramucirumab) in the second-line setting.
However, lackluster data from the dose-escalation and -expansion stages of the trial have chilled Elevation's development plans for the drug. Despite a narrower selection criteria stipulating that patients had to have CLDN18.2 expression in 20 percent or more tumor cells, as indicated by an immunohistochemistry test score of 2+ or 3+, only around 22 percent of the 36 evaluable patients responded to EO-3021 as a monotherapy, which included one confirmed complete response and seven confirmed partial responses. The disease control rate was around 72 percent.
"We are deeply disappointed by these results from our Phase I trial," Elevation CEO Joseph Ferra said in a statement. "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."
Antibody drugs and immunotherapies targeting CLDN18.2 are of growing interest to drug developers, especially after US regulators last year approved Astellas' monoclonal antibody Vyloy (zolbetuximab) plus chemotherapy as a first-line treatment for patients with locally advanced unresectable or metastatic HER2-negative CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma. There are several agents under evaluation in gastric cancer, including I-Mab's CLDN18.2 and 4-1BB bispecific antibody givastomig, Carsgen's CAR T-cell therapy satricabtagene autoleucel, and Phanes Therapeutics' CLDN18.2 and CD47 bispecific antibody PT886.
After scuttling its CLDN18.2-targeted ADC, however, Elevation is now shifting its focus to a preclinical candidate, the HER3-targeted ADC EO-1022. It hopes to file an investigational new drug application for EO-1022 in 2026.