Preclinical Activity of the B7-H3-Targeting Antibody-Drug Conjugate Vobramitamab Duocarmazine in Pediatric Solid Tumors.
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PURPOSE: Vobramitamab duocarmazine (vobra duo) is a duocarmycin-based, humanized antibody-drug conjugate (ADC) targeting B7-H3, with a drug-to-antibody ratio of ∼2.7. Vobra duo has demonstrated robust antitumor activity in multiple adult cancer models, along with favorable pharmacokinetic and safety profiles in cynomolgus monkeys. Early results from phase I/II clinical trials (NCT03729596) have shown manageable toxicity and promising objective responses in patients with metastatic castration-resistant prostate cancer. Given the high expression of B7-H3 in pediatric solid tumors, this target is emerging as a compelling therapeutic opportunity in pediatric oncology. EXPERIMENTAL DESIGN: Antitumor activity of vobra duo was evaluated in pediatric solid tumor xenograft models, including Ewing sarcoma, rhabdomyosarcoma, neuroblastoma, osteosarcoma, malignant rhabdoid tumor, hepatoblastoma, and Wilms tumor. Tumor-bearing mice received a single intraperitoneal dose of vobra duo (6 mg/kg) or a matched control ADC (SYD988, anti-CD20 ADC with an identical linker and payload). Tumor progression was defined as a fourfold increase in tumor volume. Event-free survival was analyzed using Kaplan-Meier methods, and objective responses were categorized as partial, complete, or maintained complete response. RESULTS: Vobra duo induced objective responses across multiple tumor types, whereas the control ADC showed limited activity. No clear association was observed between B7-H3 protein expression and therapeutic response. CONCLUSIONS: These findings demonstrate the broad preclinical efficacy of vobra duo in pediatric solid tumors and support further clinical investigation of B7-H3-targeted therapies in children.