A phase 1, multicenter, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of SBO-154 in subjects with advanced solid tumors.

Abstract

TPS3161 Background: Mucin 1 (MUC1) is a transmembrane glycoprotein overexpressed in advanced epithelial malignancies, where it promotes tumor progression and correlates with poor clinical outcomes. The membrane-proximal SEA domain of MUC1 is exposed on tumor cells and undergoes rapid internalization, enabling targeted intracellular delivery of cytotoxic payloads. SBO-154 is a MUC1 SEA–directed antibody–drug conjugate (ADC) conjugated to the clinically validated cytotoxic payload monomethyl auristatin E (MMAE) via a protease-cleavable linker. Unlike the shed MUC1-VNTR that creates an antigen sink limiting efficacy of prior ADCs, the negligibly shed MUC1-SEA epitope enables more effective SBO-154 tumor targeting. Nonclinical studies of SBO-154 showed MUC1-dependent cytotoxicity, dose-dependent tumor inhibition in vivo, and a favorable safety for clinical evaluation. This first-in-human study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of SBO-154 in subjects with locally recurrent or metastatic solid tumors who have exhausted or are intolerant to available therapies. Methods: This phase 1, open-label, multicenter study comprises two parts: dose escalation (Part 1) and dose expansion (Part 2). Eligible adults (≥18 years) must have RECIST v1.1–measurable, locally recurrent or metastatic solid tumors (excluding sarcoma), documented progression after or intolerance to standard therapy, ECOG performance status 0–1, adequate organ function, and tumor tissue for immunohistochemistry (IHC) analysis. SBO-154 will be administered as an intravenous infusion on Day 1 of each 21-day treatment cycle (Q3W) over 30 minutes. Part 1 will use an mTPI-2 design with intra-patient dose escalation from 0.3 mg/kg to 2.5 mg/kg. Approximately 75 subjects will be enrolled in Part 1 (~50 in dose escalation and ~25 in backfill cohorts), and up to 102 subjects in Part 2. After determining the maximum tolerated dose (MTD) and the recommended dose for expansion (RDE), Part 2 will be initiated with a Simon’s two-stage design. Planned expansion cohorts will include NSCLC, ER+ breast cancer, and ovarian cancer, with enrolment to be restricted to tumors with high MUC1-SEA expression. Treatment will continue until disease progression, unacceptable toxicity, or withdrawal from the study. Primary endpoints: include dose-limiting toxicities (DLTs), treatment-related serious adverse events, dose modifications, and clinical/laboratory safety findings. Secondary endpoints: include PK, immunogenicity and efficacy. Enrollment Status: The study initiated enrolment in August 2025. Cohorts 1 and 2 have been completed without any DLTs, and enrolment in Cohort 3 is ongoing as of December 2025. Clinical trial information: NCT07042100 .