BOSTON — Zymeworks Inc. presented preliminary results from its ongoing Phase 1 clinical study of ZW191, an antibody-drug conjugate targeting folate receptor-alpha (FRα), at the AACR-NCI-EORTC Conference on Molecular Targets and Cancer Therapeutics held October 22–26, 2025, in Boston. The investigational therapy demonstrated encouraging anti-tumor activity and a favorable safety profile across a heavily pretreated population of patients with advanced ovarian, endometrial, and non-small cell lung cancers.
As of September 10, 2025, the study had enrolled 41 patients across dose levels ranging from 1.6 to 11.2 mg/kg, with 85 percent remaining on treatment. Participants included individuals with platinum-resistant ovarian cancer, metastatic endometrial cancer, and metastatic non-small cell lung cancer, regardless of FRα expression levels.
ZW191 showed meaningful anti-tumor activity across multiple dose cohorts. Among all response-evaluable patients (n=27), the objective response rate (ORR) was 44 percent. At doses between 6.4 and 9.6 mg/kg, ORR increased to 53 percent. In patients with gynecologic cancers (n=24), ORR reached 50 percent overall and 64 percent within the 6.4–9.6 mg/kg range. Responses were observed starting at the 3.2 mg/kg dose level, including in tumors with low or negative FRα expression.
The safety profile of ZW191 was manageable, with low rates of dose modifications and delays, and few Grade 3 or higher treatment-related adverse events. No serious treatment-related adverse events, discontinuations, or deaths were reported. The most common Grade 3 or higher treatment-related events included anemia (10 percent), neutropenia (5 percent), and thrombocytopenia (5 percent). These findings support a broad therapeutic window for ZW191 and justify continued clinical development.
Following the data cut, 11.2 mg/kg was established as the maximum tolerated dose. Based on safety, efficacy, and pharmacokinetic data, two dose levels—6.4 mg/kg and 9.6 mg/kg—have been selected for further dose optimization, with approximately 30 patients planned in each cohort. The next stage of the study will further evaluate clinical activity and safety to inform a potential registrational strategy.
“We are encouraged by the early signs of anti-tumor activity and favorable safety profile in a heavily pretreated population, which supports best-in-class potential and strengthens our confidence in this approach,” said Sabeen Mekan, M.D., senior vice president of clinical development at Zymeworks.
