Zymeworks Inc. has commenced a Phase I clinical trial evaluating ZW191, an investigational antibody-drug conjugate (ADC), in patients with advanced solid tumors expressing folate receptor-α (FRα). The first patient has been dosed, marking a significant step in the development of this novel therapy for endometrial, ovarian, and non-small cell lung cancers (NSCLC).
Trial Design and Objectives
The first-in-human, multi-center, global Phase I study is designed in two parts and plans to enroll approximately 145 adult patients across sites in North America, Europe, and the Asia-Pacific region. The initial phase will focus on assessing the safety and tolerability of ZW191, including dose escalation, in subjects with advanced endometrial, ovarian, and NSCLC cancers. Secondary endpoints include evaluating pharmacokinetics and the confirmed objective response rate.
The second part of the study will further evaluate the safety of ZW191 and explore its potential anti-tumor activity in the target patient populations.
ZW191: Targeting FRα with a Novel Payload
ZW191 is engineered to target FRα, a protein frequently found on the surface of various tumor cells, including ovarian, endometrial, and lung cancers. FRα is prevalent in approximately 70% of lung adenocarcinomas and 75% of high-grade serous ovarian carcinomas.
The ADC is designed for internalization into FRα-expressing cells, facilitating the release of ZD06519, a bystander-active topoisomerase-1 inhibitor. This novel payload, developed by Zymeworks, is intended to destroy tumor cells effectively.
Preclinical Data and Rationale
Preclinical data presented at the American Association for Cancer Research (AACR) Annual Meeting demonstrated that ZW191 exhibited greater anti-tumor activity compared to standard treatments in FRα-expressing tumor models. This supports the clinical rationale for investigating ZW191 in patients with advanced solid tumors.
Executive Perspective
"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," said Jeff Smith, Zymeworks' Executive Vice President and Chief Medical Officer. "This global study represents a significant milestone in our mission to bring innovative and urgently needed therapies to patients in need."
