A phase I/IIa dose-escalation, dose-optimization, and dose-expansion study to evaluate the safety and preliminary efficacy of tri-specific antibody (SOA101) in subjects with advanced solid tumors.

Abstract

TPS2671 Background: SOA101 is a nanobody (VHH)-based tri-specific T cell engager targeting programmed death-ligand 1 (PD-L1), Human Leukocyte Antigen G (HLA-G), and Cluster of Differentiation 3 (CD3) to modulate the immunosuppressive tumor microenvironment and enhance T-cell activation and recruitment. In vitro, SOA101 showed potent, broad-spectrum anti-tumor activity, enhancing peripheral blood mononuclear cells mediated cytotoxicity against non–small cell lung cancer (NSCLC) cells with varying PD-L1/HLA-G expression. In vivo, SOA101 demonstrated superior anti-cancer efficacy compared with relevant monoclonal antibodies and bispecific T-cell engagers in a humanized NSCLC mouse model, achieving effective tumor control and prolonged survival. The pharmacologically active dose did not increase cytokine secretion ex vivo, indicating a manageable safety profile with low cytokine release syndrome risk. Methods: This first-in-human clinical study, regulated by FDA and TFDA, is being conducted in subjects with locally advanced or metastatic solid tumors, including NSCLC ovarian cancer, head and neck cancer, breast cancer, and colorectal cancer with PD-L1 expression ≥1%. The dose-escalation phase is a six-cohort study designed to determine the maximum tolerated dose or pharmacoactive dose, enrolling up to 36 subjects who receive bi-weekly SOA101 for up to six doses. The dose-optimization phase randomizes approximately 40 subjects into low- or high-dose cohorts to further evaluate safety, pharmacokinetics, preliminary antitumor activity, and to determine the recommended Phase 2 dose. Part 2 may include up to four disease-specific expansion cohorts (up to 27 subjects each) to further characterize safety and antitumor activity. The study is currently in the dose-escalation phase. Cohort 1 has been completed without DLT, and enrollment for Cohort 2 has begun following approval by the independent Safety Review Committee. Clinical Trial Registry Number: NCT07055594. Clinical trial information: NCT07055594 .