Elevation Oncology is making strides in the development of EO-3021, a Claudin 18.2-targeting antibody-drug conjugate (ADC), for the treatment of gastric and gastroesophageal junction (GEJ) cancers. Recent data from the ongoing Phase 1 clinical trial and preclinical studies suggest a promising future for this therapeutic approach, particularly in combination with other targeted therapies. The company is poised to initiate the combination arm of the Phase 1 trial in Q4 2024, building on encouraging monotherapy results and preclinical synergy data.
Promising Monotherapy Data
In August 2024, Elevation Oncology reported initial clinical data from the dose escalation portion of the Phase 1 trial of EO-3021. The data, which included patients with advanced, unresectable, or metastatic solid tumors expressing Claudin 18.2, showed an objective response rate (ORR) of 42.8% in patients with Claudin 18.2 expression in ≥20% of tumor cells at IHC 2+/3+. This ORR was observed in a subset of seven patients with gastric and GEJ cancer. The disease control rate (DCR) in this group was 71.4%, including two patients with stable disease. Importantly, EO-3021 was generally well-tolerated, with minimal hematological toxicity or hepatotoxicity, and no peripheral neuropathy/hypoesthesia observed in the safety population of 32 patients. These initial safety data suggest minimal payload-associated toxicity and limited overlapping toxicity with standard-of-care agents, including PD-1 inhibitors and chemotherapies.
Preclinical Evidence for Combination Therapy
Further bolstering the potential of EO-3021, preclinical data presented at the European Society for Medical Oncology Immuno-Oncology Annual Congress 2024 (ESMO-IO) demonstrated synergistic anti-tumor activity when EO-3021 was combined with either a VEGFR2 inhibitor (ramucirumab surrogate, DC101) or a PD-1 inhibitor. In vivo studies showed that the combination of EO-3021 and DC101 resulted in statistically superior tumor growth inhibition (TGI) compared to either agent alone (TGI: 88.2% for the combination vs. 20.1% for EO-3021 and 59.2% for DC101 alone). Similarly, the combination of EO-3021 and a PD-1 inhibitor exhibited statistically superior TGI compared to monotherapy (TGI: 79.9% for the combination vs. 33.8% for EO-3021 and 25.0% for the PD-1 inhibitor alone). Notably, 92% of mice treated with the EO-3021 and PD-1 inhibitor combination achieved a complete response (CR), compared to 50% with EO-3021 alone and 17% with the PD-1 inhibitor alone.
Clinical Trial Plans and Regulatory Status
Based on these promising data, Elevation Oncology is set to initiate dosing in the combination portion of its ongoing Phase 1 clinical trial of EO-3021 in Q4 2024. The trial will evaluate EO-3021 in combination with ramucirumab, a VEGFR2 inhibitor, in second-line gastric/GEJ cancer patients, and in combination with dostarlimab, a PD-1 inhibitor, in the front-line setting. In September 2024, the FDA granted Fast Track designation to EO-3021 for the treatment of patients with advanced or metastatic gastric and GEJ cancer expressing Claudin 18.2 that has progressed on or after prior therapy. This designation is designed to expedite the development and review of therapeutic candidates that address serious conditions with unmet medical needs. EO-3021 also holds orphan drug designation from the FDA for the treatment of gastric cancer (including cancer of the gastroesophageal junction) and pancreatic cancer.
Financial Position and Future Outlook
Elevation Oncology's financial position remains strong, with $103.1 million in cash, cash equivalents, and marketable securities as of September 30, 2024. The company anticipates that these funds will be sufficient to support its operations into 2026. With ongoing clinical trials and a robust preclinical program, Elevation Oncology is focused on advancing EO-3021 and its HER3-ADC program to address significant unmet needs in cancer treatment.
