2029TiP Phase I study of ABBV-706, an anti-SEZ6 antibody-drug conjugate, alone or in combination in adults with advanced solid tumors

Seizure-related 6 homolog (SEZ6) is overexpressed in many tumor types with high unmet need, including small cell lung cancer (SCLC), neuroendocrine carcinomas (NECs), and central nervous system (CNS) tumors. ABBV-706 is an antibody-drug conjugate (ADC) comprised of an anti-SEZ6 antibody conjugated to a topoisomerase 1 inhibitor payload. This is an open-label, phase 1, first-in-human, dose-escalation, and expansion study (NCT05599984). 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. The study has 4 parts: (1) ABBV-706 monotherapy dose escalation in relapsed or refractory (R/R) solid tumors, following the Bayesian optimal interval (BOIN) design; (2) monotherapy dose optimization, randomized between two or more dose levels, and expansion in R/R SCLC; (3) dose escalation and expansion of ABBV-706 in combination with budigalimab or platinum therapy in R/R SCLC and NECs; (4) monotherapy dose expansion in R/R high-grade CNS tumors or NECs. Safety endpoints include adverse events, clinical laboratory tests, vital signs, and dose-limiting toxicities. PK endpoints include Cmax, tmax, t1/2, and AUC. Primary efficacy endpoints include objective response rate and duration of response. Clinical benefit rate, progression-free survival, overall survival, and biomarkers will also be evaluated. ABBV-706 will be administered intravenously until disease progression, withdrawal of consent, or unacceptable toxicity. Trial Eligibility: adults ≥18 years old with R/R SCLC, NECs (including neuroendocrine prostate cancer), or high-grade CNS tumors and measurable disease per RECIST v1.1 or RANO, with an ECOG score ≤1. Tumor tissue submission for retrospective SEZ6 expression analysis is required. The study began in December 2022 and enrollment is ongoing. NCT05599984. Medical writing support was provided by Heather Hultzapple, Pharm D of Fishawack Ltd, funded by AbbVie, Inc. AbbVie. ABBV-706 is being developed by AbbVie. AbbVie funded this study and participated in the study design, as well as the writing, review, and approval of the publication. No honoraria or payments were made for authorship.