Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Preclinical Activity of the B7-H3-Targeting Antibody-Drug Conjugate Vobramitamab Duocarmazine in Pediatric Solid Tumors.
СтатьяНазвание и аннотация: Перевод в очереди
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Favours Edward, Tang Haiying, Wong Peyton, Ghilu Samuel, Del Pozo Vanessa, Mironova Elena, Chen Yidong, Stearns Tim, Neuhauser Steven, Earley Eric J, Erickson Stephen W, Kwon Jee Young, Jocoy Emily L, Groff David, Krytska Kateryna, Tsang Matthew, Teicher Beverly A, Mossé Yael P, Kolb E Anders, Hav Monirath, Loo Deryk, Houghton Peter J, Bult Carol J, Gorlick Richard G, Maris John M, Smith Malcolm A, Kurmasheva Raushan T
Аннотация
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.
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.