Safety and efficacy of ABBV-706, a seizure-related homolog protein 6 (SEZ6)–targeting antibody-drug conjugate, in high-grade neuroendocrine neoplasms.

作者：Alissa J. Cooper, Sreenivasa R Chandana, Muhammad Furqan, Kyriakos P. Papadopoulos, Afshin Dowlati, Ji‐Youn Han, Michael Michael, Byoung Chul Cho, Benjamin Garmezy, Tae Min Kim, Anne C. Chiang, Jair Bar, Noura J. Choudhury, Wallace Akerley, Sunil Babu, Wijith Munasinghe, Randy Robinson, Fred Kohlhapp, Pooja Hingorani, Lauren A. Byers · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.105 · 被引用次数：9 · 研究领域：Neuroendocrine Tumor Research Advances、Neuroblastoma Research and Treatments、HER2/EGFR in Cancer Research

105 Background: SEZ6 is a potential neuroendocrine lineage marker that is expressed in small cell lung cancer (SCLC) and high-grade neuroendocrine neoplasms (NENs). NENs have a significant unmet need for novel effective targeted therapies. ABBV-706, a unique antibody-drug conjugate comprising a SEZ6-directed antibody conjugated to a potent topoisomerase 1 inhibitor payload, is being evaluated in a phase 1 study (NCT05599984) in patients (pts) with advanced solid tumors. Preliminary results from ABBV-706 monotherapy dose escalation showed a manageable safety profile with promising efficacy in SCLC and NENs ( J Clin Oncol 2024;42[suppl 16]: abs 3001). Herein, updated safety and efficacy of ABBV-706 monotherapy in NENs are presented. Methods: Pts (≥18 yr) with relapsed/refractory high-grade NENs (well-differentiated grade [G] 3 neuroendocrine tumors [G3 NETs] and poorly differentiated neuroendocrine carcinomas [NECs]), atypical lung carcinoid, and medullary thyroid cancer (MTC) were enrolled in dose-escalation and -expansion cohorts of a phase 1, open-label study. Pts received ABBV-706 monotherapy IV at 1.3–3.5 mg/kg once every 3 weeks. Primary study objectives are assessment of safety, PK, and efficacy. SEZ6 expression is evaluated retrospectively. Results: As of Aug 27, 2024, 191 pts were enrolled overall, including 64 with NENs. In the NEN cohort, median age was 63 yr (range 33–86) and pts had received a median of 3 (range 1–8) prior therapies. NEN histologies were large cell...