Zymeworks to discontinue clinical development of ZW171

Zymeworks (ZYME) announced its decision to voluntarily discontinue clinical development of ZW171, a T cell engager designed to target gynecological, thoracic, and digestive system cancers. ZW171 is designed to address cancers driven by mesothelin, a well-recognized but historically challenging target. The decision to discontinue clinical development of ZW171 was based on completion of the planned cohorts of the dose escalation portion of the Phase 1 trial of ZW171 in patients with ovarian cancer and non-small cell lung cancer. After completing the planned dose escalation cohorts and establishing a maximum tolerated dose, Zymeworks determined that further dose evaluation in the current trial would be unlikely to support a benefit-risk profile consistent with the desired monotherapy target product profile. While cytokine release syndrome was well-managed in the Phase 1 study, dose-limiting toxicities were consistent with mesothelin-related on-target off-tumor toxicity. Ongoing participants in the Phase 1 trial will continue treatment at the discretion of their investigator, and participants who have discontinued treatment will continue safety follow-up as per the study protocol. “While this is a disappointing outcome given the promising preclinical activity observed with ZW171, we are deeply grateful to the patients, providers, and caregivers for their support and participation in the ZW171 Phase 1 study,” said Kenneth Galbraith, Chair and Chief Executive Officer of Zymeworks. “As part of Zymeworks’ disciplined approach to the management of our broad product portfolio, we are committed to careful and consistent evaluation of clinical progress for each product candidate to ensure our resources are directed towards those product candidates with the greatest potential impact for patients. We continue to advance our broader product pipeline, including the ongoing Phase 1 trial of ZW191 and the initiation of a Phase 1 study for ZW251 expected in 2025. We are also preparing an IND filing for ZW209, our DLL3-directed trispecific T cell engager, planned in the first half of 2026.”