Elevation Oncology (ELEV) Study Update summary

Key study results and insights

• EO-3021, a Claudin 18.2-targeted ADC, showed a confirmed objective response rate (ORR) of 42.8% and disease control rate (DCR) of 71.4% in Claudin 18.2-enriched gastric and GEJ cancer patients (≥20% tumor cells at IHC 2+/3+); no responses were seen in patients with lower expression, underscoring the importance of biomarker selection.

• All observed responses were partial and ongoing, limited to patients with high Claudin 18.2 expression.

• EO-3021 demonstrated a favorable safety profile, with minimal MMAE-associated toxicities, no neutropenia or peripheral neuropathy, and no Grade 4/5 treatment-related adverse events; most common adverse events were nausea, decreased appetite, fatigue, and diarrhea.

• Dose-limiting toxicities at the highest dose (2.9 mg/kg) led to selection of 2.0 and 2.5 mg/kg for further study; less than 10% discontinued due to adverse events.

• EO-3021 is considered suitable for combination regimens due to its tolerability and differentiated safety profile.

Study design and patient population

• The Phase 1 trial enrolled 32 patients in dose escalation (1.0–2.9 mg/kg Q3W), including 26 with gastric or GEJ cancer; median age was 65, with a heavily pretreated population (median three prior therapies, 81% prior PD-1/PD-L1 exposure).

• Efficacy was evaluated in patients with measurable disease and available Claudin 18.2 IHC results; patients were bifurcated by Claudin 18.2 expression to assess response correlation.

• Claudin 18.2 expression was retrospectively assessed; biomarker-driven patient selection is central to ongoing and future development.

• The study included patients with advanced, unresectable, or metastatic solid tumors likely to express Claudin 18.2, including gastric, GEJ, pancreatic, or esophageal cancers.

• Less than 10% discontinued due to adverse events.

Mechanism and differentiation

• EO-3021 is a site-specifically conjugated ADC targeting Claudin 18.2, using glutamine 295 conjugation for increased stability and reduced free MMAE exposure compared to traditional ADCs.

• Pharmacokinetic data showed higher ADC exposure and lower free MMAE, supporting improved safety.

• The ADC's bystander effect may allow efficacy in tumors with lower Claudin 18.2 expression.

• EO-3021 may offer broader applicability and better tolerability than monoclonal antibodies, bispecifics, or CAR T therapies.

• The safety profile, especially lack of bone marrow suppression and severe neuropathy, is a key differentiator.