Abstract 7815: Efficacy of ABBV-706, a SEZ6-targeted topoisomerase 1 inhibitor ADC: A report from the Pediatric Preclinical In Vivo Testing (PIVOT) Program

Abstract Introduction: ABBV-706 is an antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting the seizure-related homolog 6 (SEZ6) surface protein linked to topoisomerase 1 inhibitor payload. A Phase 1 trial of ABBV-706 is underway in adults with SEZ6 expressing relapsed solid tumors (NCT05599984). ABBV-706 became of interest as SEZ6 is highly expressed in many pediatric cancers. The goal was to evaluate ABBV-706 in models of childhood cancers with notable SEZ6 expression: neuroblastoma (NB), medulloblastoma (MB), retinoblastoma (RB), and alveolar rhabdomyosarcoma (ARMS) and compare the activity to vehicle and isotype non-target control ADC (IC-ADC). Methods: Pediatric xenograft models were screened for SEZ6 expression. Single agent in vivo studies were completed in NB, MB, RB, and ARMS models with varying SEZ6 expression. After engraftment, 2 total doses of ABBV-706 or IC-ADC were given by IP injection 3 weeks apart at 2 dose levels (DL1, DL2). Efficacy was assessed by median event free survival (KM med, in days) and objective response measure (Ped Blood Cancer 2007;49:928-940). ORM defines an objective response as partial, complete, or maintained complete response (PR, CR, and MCR) compared to stable disease (SD) or progressive disease, with or without growth delay (PD2 and PD1, respectively). Results: ABBV-706 showed efficacy in a broad range of SEZ6 expressing non-CNS (NB, RB, ARMS) models. At DL1, PR, CR, or MCR responses were seen in 8 of 11 models. At DL2, 9 of 11 models had PR, CR, or MCR responses. For most models, ABBV-706 was more active than IC-ADC. Survival advantage was observed in 1 of 2 MB models. Conclusion: We showed high anti-tumor activity for ABBV-706 in multiple SEZ6 expressing models and enhanced efficacy versus IC-ADC. Due to high expression of SEZ6 in several pediatric histologies, ABBV-706 has potential for clinical activity in patients with these cancers. Citation Format: Elizabeth A. Stewart, Michael A. Dyer, Yael P. Mosse, John M. Maris, Xiao-Nan Li, Stefan Atkinson, Chen He, David N. Groff, Alvin Farrel, Yuchen Du, Jinnan Chen, Steven B. Neuhauser, Timothy M. Stearns, Emily L. Jocoy, Jee Young Kwon, Jeffrey H. Chuang, Emily Faivre, Kelly Doyle, Kimberly E. Ellison, Joshua F. Hernandez, Joann P. Palma, Michael Barnes, Pooja Hingorani, Nandini Rudra-Ganguly, Beverly A. Teicher, Carol J. Bult, Malcolm A. Smith. Efficacy of ABBV-706, a SEZ6-targeted topoisomerase 1 inhibitor ADC: A report from the Pediatric Preclinical In Vivo Testing (PIVOT) Program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7815.