FDA Grants FTD to EO-3021 in Advanced Gastric and GEJ Cancers Expressing Claudin 18.2

• The FDA granted fast track designation (FTD) to EO-3021 in advanced or metastatic gastric and gastroesophageal junction (GEJ) cancer expressing Claudin (CLDN) 18.2 that has progressed on or after prior therapy.
• EO-3021 is a differentiated, clinical-stage antibody-drug conjugate (ADC).
• A phase 1 study (NCT05980416) is evaluating EO-3021 in patients with advanced, unresectable or metastatic solid tumors likely to express CLDN18.2 including gastric, GEJ, pancreatic, or esophageal cancers.

EO-3021, a differentiated ADC in development for the treatment of patients with advanced or metastatic gastric and GEJ cancer expressing CLDN18.2 that has progressed on or after prior therapy, was granted FTD from the FDA.¹

The clinical-stage ADC with best-in-class potential consists of a monoclonal IgG1 antibody targeting CLDN18.2, a protein primarily found in gastric epithelial cells but exposed during malignant transformation due to disruption of tight junctions. EO-3021 delivers a monomethyl auristatin E (MMAE) cytotoxic payload via a cleavable linker, site-specifically conjugated to Glutamine 295, yielding a drug-to-antibody ratio of 2.

EO-3021 is currently under investigation in a phase 1 clinical trial in patients with advanced, unresectable, or metastatic solid tumors likely to express CLDN18.2, including gastric, GEJ, pancreatic, and esophageal cancers.

Gastric/GEJ tumor: ©LASZLO - stock.adobe.com

"We are delighted to receive fast track designation for EO-3021, which marks an encouraging recognition of the unmet medical need in patients with Claudin 18.2-expressing tumors, as well as the potential for EO-3021 to deliver improved therapeutic outcomes," said Joseph Ferra, president and chief executive officer of Elevation Oncology, in a press release. "This designation is based on nonclinical and initial clinical data from our ongoing phase 1 clinical trial. As we announced in August, early results showed a confirmed overall response rate of 42.8% in a Claudin 18.2-enriched subset of gastric and GEJ cancer. In addition, we observed differentiated tolerability, with minimal MMAE-associated toxicities, including no neutropenia or peripheral neuropathy/hypoesthesia.”

“We are grateful for the opportunity to potentially expedite the delivery of EO-3021 and look forward to advancing through monotherapy dose expansion and reporting additional data from our ongoing trial in the first half of 2025, and to initiating the combination portion of our study later this year," continued Ferra.

About the Phase 1 Study of EO-3021

In the open-label, international, multicenter, phase 1 study, experts are evaluating EO-3021 as a treatment for adult patients with solid tumors likely to express CLDN18.2.²

In the escalation phase of the study (part A), adult patients with select advanced unresectable or metastatic solid tumors likely to express CLDN18.2 will receive EO-3021 given via intravenous (IV) infusion at various doses every 3 weeks to determine the maximum tolerated doses or recommended phase 2 dose (RP2D) of the study. In the expansion part (part B), those with select advanced unresectable or metastatic solid tumors will receive IV EO-3021 every 3 weeks to confirm the RP2D.

Patients aged 18 years and older with an ECOG performance status of 0 or 1 at screening with select advanced or metastatic solid tumors that are likely to express CLDN18.2 are eligible for enrollment in the study. Enrollment is also open to those who have tumor tissue available; have progressed on or after standard therapy ; are intolerant to available standard therapy, or have no available standard therapy; and have at least 1 measurable extracranial lesion as defined by RECIST v1.1. Additional requirements for enrollment include having adequate organ function and a life expectancy at least 12 weeks.

The primary end points include incidence rate of dose limiting toxicities during the first 21-day cycle of EO-3021 treatment, number of patients with treatment-emergent adverse effects (AEs), number of patients with serious AEs, number of patients with clinically significant changes to vital signs, and number of patients with clinically significant changes in laboratory tests.

REFERENCES:

1. Elevation Oncology receives fast track designation from the FDA for EO-3021 for the treatment of adult patients with advanced or metastatic gastric or gastroesophageal junction cancer expressing claudin 18.2. News release. Elevation Oncology, Inc. September 23, 2024. Accessed September 23, 2024. https://tinyurl.com/shkdejzt

2. Study of EO-3021 in adult patients with solid tumors likely to express CLDN18.2. ClinicalTrials.gov. July 12, 2024. Accessed September 23, 2024. https://clinicaltrials.gov/study/NCT05980416