Abstract 7040: The B7-H3 targeting antibody-drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) is potently effective against a broad panel of pediatric solid tumor xenograft models: A study from the Pediatric Preclinical In Vivo Testing (PIVOT) Consortium

Vobra duo, a duocarmycin-based humanized ADC (drug-to-antibody ratio is ∼2.7) targeting B7-H3, shows robust in vivo activity against a range of adult cancer models, and a favorable pharmacokinetic and safety profile in cynomolgus monkeys. Initial results from the single agent phase 1 clinical trial of vobra duo (NCT03729596) showed manageable side effects and promising objective response rates in metastatic castration-resistant prostate cancer. B7-H3 is highly expressed in pediatric solid tumors, and it is emerging as a key target for pediatric oncology. Here we report the antitumor activity of vobra duo against preclinical xenograft models of pediatric solid tumors. Ewing sarcoma (ES), rhabdomyosarcoma (RMS), and neuroblastoma (NB) xenograft models were tested with n=1 or n=2 designs. Osteosarcoma (OS) models, due to their slower growth kinetics and lower rates of tumor regression, were tested with n=10 mice per arm. The study was extended to include malignant rhabdoid tumor (MRT), hepatoblastoma (HB), and Wilms tumor (WT) models using n=5 mice per treatment group. vobra duo and control ADC (SYD988 anti-CD20 ADC with the same linker and payload as vobra duo) were provided by MacroGenics, Inc., and were administered at 6 mg/kg as a single administration IP. Time-to-event was defined as 4-fold increase in tumor xenograft volume from the day of treatment. The Kaplan-Meier method was used to compare event-free survival (EFS) between treated and control groups. Objective response categories were determined as described previously (Ped Blood Cancer 2007;49:928-940), with objective responses including partial, complete, and maintained complete responses (PR, CR, and MCR). Vobra duo induced objective responses in 4 of 11 NB models (3 CR and 1 MCR) and in 3 of 5 OS models (2 MCR). ES models showed objective responses in 2 of 6 models (1 MCR) and 4 of 6 RMS models showed objective responses, all MCR. Control ADC was less active than vobra duo and showed objective responses in 0 of 11 NB, 1 of 5 OS, 1 of 6 ES, and 2 of 4 RMS models. The study was extended to MRT, HB, and WT models. Vobra duo induced objective responses in 2 of 4 MRT with 1 MCR, 2 of 5 HB with 2 MCR, and 3 of 4 WT with 3 MCR. Control ADC only induced objective responses in 1 of 4 MRT and 2 of 4 WT models (all PR), with no objective responses for the 5 HB models. Vobra duo is potently efficacious across a broad panel of pediatric solid tumor xenograft models supporting clinical development of this agent and other agents targeting B7-H3 for children with cancer. Haiying Tang, Edward Favours, Samson Ghilu, Peyton Wong, Vanessa Del Pozo, Abhik Bandyopadhyay, Elena Mironova, Eric J. Earley, Stephen W. Erickson, David Groff, Beverly A. Teicher, Kateryna Krytska, Matthew Tsang, Yael P. Mosse, E. Anders Kolb, Matthew Stephens, Steve Neuhauser, Tim Stearns, Jeff Chuang, Emily L. Jocoy, Jee Young Kwon, Carol Bult, Malcolm A. Smith, John M. Maris, Richard G. Gorlick, Peter J. Houghton, Raushan Kurmasheva. The B7-H3 targeting antibody-drug conjugate (ADC) vobramitamab duocarmazine (vobra duo) is potently effective against a broad panel of pediatric solid tumor xenograft models: A study from the Pediatric Preclinical In Vivo Testing (PIVOT) Consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7040.