Seizure-related homolog 6 (SEZ6) is expressed in small cell lung cancer (SCLC) and neuroendocrine neoplasms. In an open label, phase 1 trial, ABBV-706, an antibody−drug conjugate with a SEZ6-directed antibody linked to topoisomerase-1 inhibitor (Top1i), was administered intravenously every 3 weeks (Q3W) to 288 patients with advanced solid tumors; 240 received monotherapy, including 124 with relapsed/refractory (R/R) SCLC.
Primary objectives of dose escalation (part 1, advanced solid tumors), dose optimization and expansion (part 2, R/R SCLC only) and dose expansion (part 4, central nervous system tumors and high-grade neuroendocrine neoplasms only) were to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity and antitumor activity of ABBV-706 monotherapy and, from parts 1 and 2, to determine the recommended phase 2 dose (RP2D) of ABBV-706 in R/R SCLC. In the monotherapy cohort ( N = 240), the most common treatment-related adverse events (TRAEs) at any grade were anemia (61%) and fatigue (38%).
Grade 3 or higher TRAEs occurred in 61% of patients and were dose dependent (39% at 1.8 mg kg −1 and 70% at 2.5 mg kg −1 ).
Nature Medicine published a clinical update in Research Highlights on 01 Jun 2026.
The item focuses on SEZ6-targeting antibody−drug conjugate ABBV-706 in advanced small cell lung cancer and solid tumors: a phase 1 trial.
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