Zymeworks Inc. has announced the dosing of the first patient in a Phase 1 clinical trial evaluating ZW191, a novel antibody-drug conjugate (ADC), for the treatment of advanced folate receptor-α (FRα)-expressing solid tumors. The trial, registered as NCT06555744, aims to assess the safety and tolerability of ZW191 in patients with cancers such as ovarian, endometrial, and non-small cell lung cancer (NSCLC). This first-in-human study marks a significant step in Zymeworks' mission to develop innovative therapies for difficult-to-treat cancers.
Targeting Folate Receptor-α in Solid Tumors
ZW191 is designed to target FRα, a protein highly expressed on the surface of various tumors. FRα is found in approximately 75% of high-grade serous ovarian carcinomas and about 70% of lung adenocarcinomas. Preclinical data presented at the American Association for Cancer Research (AACR) Annual Meeting in 2024 indicated that ZW191 demonstrated greater anti-tumor activity compared to benchmark treatments in FRα-expressing tumor models and was well-tolerated in preclinical studies involving cynomolgus monkeys at doses up to 60 mg/kg.
Trial Design and Objectives
The Phase 1 trial is a two-part, multi-center, global study planning to enroll 145 adult patients with advanced FRα-expressing cancers. The study will be conducted across sites in North America, Europe, and the Asia-Pacific region. The first part of the trial will focus on evaluating the safety and tolerability of ZW191 through dose escalation in patients with advanced ovarian, endometrial, and NSCLC cancers. Secondary endpoints include assessing pharmacokinetics and confirmed objective response rate. The second part of the study will further evaluate the safety profile and explore the potential anti-tumor activity of ZW191.
About ZW191
ZW191 is an ADC engineered to target FRα. Its design facilitates internalization into FRα-expressing cells, potentially releasing ZD06519, a novel proprietary topoisomerase-1 inhibitor developed by Zymeworks, to induce tumor cell death. This mechanism of action aims to provide a targeted approach to cancer therapy, minimizing off-target effects and maximizing efficacy.
Jeff Smith, M.D., FRCP, Executive Vice President and Chief Medical Officer at Zymeworks, stated, “Our team is excited to initiate this important clinical trial to assess the safety and tolerability of ZW191, our first antibody-drug conjugate utilizing ZD06519, our novel proprietary payload, in patients with difficult-to-treat cancers. This global study represents a significant milestone in our mission to bring innovative and urgently needed therapies to patients in need.”
