Preclinical activity of the b7-h3- targeting antibody-drug conjugate (adc) vobramitamab duocarmazine (vobra duo) in pediatric solid tumors

Abstract

INTRODUCTION: 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.

METHODS: 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 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 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 broad preclinical efficacy of vobra-duo in pediatric solid tumors and support further clinical investigation of B7-H3-targeted therapies in children.