Mecbotamab vedotin (CAB-AXL-ADC) delivers 17.6-mo median OS in heavily pretreated bone sarcomas

Mecbotamab vedotin (Mec‑V; BA3011) is a low-pH conditionally binding AXL-targeted antibody–drug conjugate (ADC) designed to preferentially engage AXL in the acidic tumor microenvironment and limit off-tumor toxicity. In an open-label Phase 1/2 study (NCT03425279), AXL-expressing unresectable/metastatic osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma patients received Mec‑V 1.8mg/kg IV Q2W (n=33; median 2 prior lines), with median OS 17.6 months overall (osteosarcoma 11.9; Ewing 19.4; chondrosarcoma NE; chordoma 15.1) and DCR 50% in osteosarcoma/Ewing (3 confirmed responses; 14%) vs 100% DCR in chondrosarcoma/chordoma (small n). Toxicity was mostly low-grade/reversible (64%); key Grade 3/4 related TEAE was neutropenia (18%) with no Grade 5 events—against salvage Ewing benchmarks like irinotecan/temozolomide reporting median OS ~13.9 months in prospective data, this OS signal looks directionally competitive, though cross-trial comparisons are fragile and histology mix matters.