Overall survival analysis of a heavily pretreated population of patients with bone sarcomas treated with mecbotamab vedotin, a conditionally binding ADC targeting AXL.

11511 Background: Patients with metastatic bone sarcomas continue to lack effective therapies. AXL, a cell-surface receptor tyrosine kinase, is highly expressed in bone sarcoma subtypes and has been shown to drive increased metastasis, resistance to chemotherapy, and poor outcomes. Mecbotamab vedotin (Mec-V, BA3011, Conditionally Active Biologic CAB-AXL-ADC) is designed to reduce off-tumor toxicity and improve pharmacokinetics by conditionally binding to AXL under low-pH conditions (pH<6.7) of the tumor microenvironment. Methods: A phase 1/2 open-label study evaluated Mec-V among adult and adolescent patients with AXL-expressing locally advanced, unresectable, or metastatic osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma with measurable disease by RECIST v1.1. Patients received Mec-V monotherapy intravenously 1.8 mg/kg every 2 weeks (Q2W). Results: This report focuses upon the long term follow up among 33 patients treated with Mec-V with osteosarcoma (n=13), Ewing (n=9), chondrosarcoma (n=8) or chordoma (n=3). Patients received a median of 2 prior lines of treatment. Most related treatment-related adverse events (TEAE) in patients with bone sarcomas were low grade (64%) and reversible; the most common related grade 3/4 TEAE of special interest was neutropenia (18%). No grade 5 TEAE were observed. As of March 25, 2025, disease control rate (DCR) was 100% among patients with chondrosarcoma and chordoma. In patients with osteosarcoma and Ewing sarcoma, DCR was 50% with 3 confirmed responses (14%; osteosarcoma n=2, Ewing n=1). The median OS with Mec-V for all bone sarcoma patients was 17.6 months. Observed median OS by tumor type in months: osteosarcoma (11.9 [95% CI: 3.2-Not Estimable (NE)]), Ewing sarcoma (19.4 [95% CI: 5.2–NE]), chondrosarcoma (NE [95% CI: 16.3-NE]), and chordoma (15.1 [95% CI: 7.2-NE]). Conclusions: Patients with treatment refractory bone sarcomas treated with Mec-V monotherapy achieved a median OS of 17.6 months which compares favorably to reported outcomes with other therapies including combination therapies. Mec-V monotherapy holds considerable promise for these high unmet need indications with potential increased benefit when used in combination. Clinical trial information: NCT03425279 .