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Safety and efficacy of ABBV-706, a seizure-related homolog protein 6 (SEZ6)-targeting antibody-drug conjugate, in high-grade neuroendocrine neoplasms
Abstract   Open access   Peer reviewed

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

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, …
Journal of clinical oncology, Vol.43(16_suppl), pp.105-105
06/01/2025
DOI: 10.1200/JCO.2025.43.16_suppl.105
url
https://doi.org/10.1200/JCO.2025.43.16_suppl.105View
Published (Version of record) Open Access

Abstract

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 NEC (LCNEC; 22%, n=14), gastro-enteropancreatic NEC (GEPNEC; 19%, n=12), MTC (9%, n=6), neuroendocrine prostate carcinoma (NEPC; 8%, n=5), G3 NETs (8%, n=5), and other NECs (34%, n=22). The safety profile for ABBV-706 was similar across NEN subtypes and aligned with the entire study population. For the overall study population, TEAEs occurred in 184 (96%) pts and G≥3 in 134 (70%). Most frequent hematologic TEAEs were anemia (58%; G≥3: 45%), neutropenia (44%; G≥3: 33%), and thrombocytopenia (35%; G≥3: 21%). Most frequent nonhematologic TEAEs were fatigue (45%; G≥3: 3%) and nausea (38%; G≥3: 2%). Unadjudicated pneumonitis/interstitial lung disease rate was 4% (G≥3 in 2 pts). For the entire NEN cohort, the objective response rate (ORR) was 31.3% (20/64) and the clinical benefit rate was 92.2% (59/64). ORR by NEN type was: LCNEC, 28.6% (4/14); GEPNEC, 16.7% (2/12); NEPC, 60.0% (3/5); G3 NET, 60% (3/5); MTC, 16.7% (1/6); other NEC, 31.8% (7/22). The median duration of response was 5.59 mo (95% CI: 4.24, not estimable) and median progression-free survival was 6.80 mo (95% CI: 5.45, 7.75). Correlation analysis of efficacy with SEZ6 expression is ongoing. Conclusions: ABBV-706 showed preliminary efficacy in several high-grade NENs with a high unmet need, supporting its further development in specific subtypes. Clinical trial information: NCT05599984.

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