SEZ6 may serve as a novel biomarker for MTCs. Although SEZ6 lacks any prognostic values in MTC, its positivity in 91% to 93% of MTCs, including MTCs without RET and RAS mutations, renders SEZ6-targetted antibody-drug conjugate therapy a promising targeted therapy for MTCs.

ABBV-011 1.0 mg/kg Q3W monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation.

P1, N=350, Recruiting, AbbVie | Trial completion date: Oct 2025 --> May 2027

P1, N=350, Recruiting, AbbVie | Trial completion date: Dec 2026 --> Oct 2025 | Trial primary completion date: Dec 2026 --> Oct 2025

P1, N=132, Completed, AbbVie | Active, not recruiting --> Completed

Significance Statement Several in vitro and in vivo stability studies of ABBV-011, a calicheamicin-based ADC, identified circulating metabolites and catabolites and suggested that disulfide cleavage may be a key liability for the conjugated linker-payload. These observations may be relevant to other disulfide-linked ADCs, such as Mylotarg and Besponsa, both of which have reported similar half-lives that possibly indicate instability.

P1, N=45, Completed, Guangzhou JOYO Pharma Co., Ltd

P2/3, N=210, Recruiting, Guangzhou JOYO Pharma Co., Ltd

The study will evaluate the preliminary safety, tolerability, pharmacokinetics (PK), and antitumor activity of ABBV-706 as monotherapy and in combination with budigalimab (a PD-1 inhibitor), carboplatin, or cisplatin, and determine the recommended phase 2 dose (RP2D) of ABBV-706. Tumor tissue submission for retrospective SEZ6 expression analysis is required. The study began in December 2022 and enrollment is ongoing.

P1, N=132, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting | N=233 --> 132