A phase I, first-in-human study to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activities of GenSci139 in patients with solid tumors.

Abstract

TPS4638 Background: HER2 and EGFR are frequently co-expressed in solid tumors. Bispecific targeting of these receptors can produce synergistic enhancement in cell binding and internalization, potentially overcoming monotherapy resistance and maintaining efficacy in low antigen-expression settings. GenSci139 is a bispecific antibody-drug conjugate (ADC) directed against both EGFR and HER2, incorporating a cleavable linker to deliver a topoisomerase I inhibitor. In preclinical studies, GenSci139 demonstrated broad-spectrum efficacy, surpassing ENHERTU in HER2-low tumor models. It also displayed a favorable pharmacokinetic and a tolerable safety profile. These findings support further clinical evaluation of GenSci139 in urothelial carcinoma (UC), non-small cell lung cancer (NSCLC), gastric cancer (GC), triple-negative breast cancer (TNBC) and other EGFR/HER2-driven malignancies. Methods: This first-in-human, open-label study (NCT07230977) comprises a dose escalation phase with backfill (Part 1) and a dose expansion phase (Part 2). Part 1 employs an accelerated titration followed by a “3+3” design to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE). Backfill cohorts will be enrolled at selected dose levels according to predefined criteria. Part 2 will further evaluate preliminary antitumor activities in predefined cohorts. Key eligibility criteria include advanced solid tumors, measurable disease per RECIST1.1, adequate hematologic and organ function, being able to provide tumor tissues. GenSci139 is administered intravenously every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, initiation of alternative anticancer therapy, or other discontinuation criteria are met. Primary endpoints in Part 1 include the incidence of dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs). After determination of the MTD/RDE, Part 2 will evaluate the preliminary anti-tumor activity of GenSci139, with primary endpoints including objective response rate (ORR), disease control rate (DCR) and Duration of response (DoR). The study initiated in December 2025 and is currently recruiting. Clinical trial information: NCT07230977 .