At the ESMO Congress 2026, Jung-Yun Lee (Seoul, Republic of Korea) presented results from the ongoing first-in-human ZWI-ZW191-101 trial (NCT06555744), evaluating ZW191, a folate receptor alpha (FRα)-targeted antibody–drug conjugate (ADC), in patients with heavily pretreated platinum-resistant ovarian cancer.
The investigational therapy demonstrated encouraging antitumor activity, achieving an objective response rate (ORR) of 58% at both evaluated dose levels among response-evaluable patients with non-clear-cell ovarian cancer.
Methods
ZWI-ZW191-101 is an ongoing first-in-human study evaluating the safety, tolerability, and antitumor activity of ZW191 in patients with platinum-resistant ovarian cancer.
Eligible patients had experienced disease progression following available systemic therapies and were enrolled regardless of tumor histology, FRα expression, or number of previous treatment lines.
The combined analysis included patients from Part 1 dose escalation and Part 2 randomized dose optimization. In Part 2, patients were randomized 1:1 to receive intravenous ZW191 at either 6.4 mg/kg or 9.6 mg/kg every three weeks.
A total of 80 patients received treatment, including 37 at 6.4 mg/kg and 43 at 9.6 mg/kg. The median age was 61 years, and patients had received a median of four prior lines of systemic therapy.
Previous treatments included platinum and taxane chemotherapy (100%), bevacizumab (84%), PARP inhibitors (56%), and immune checkpoint inhibitors (19%).
Key Takeaways
At the July 17, 2026, data cutoff, the median follow-up was five months.
- Objective response rate: 58% at both 6.4 mg/kg and 9.6 mg/kg among response-evaluable patients with non-clear-cell ovarian cancer.
- Confirmed objective response rate: 52% at 6.4 mg/kg and 45% at 9.6 mg/kg, with 48% overall in the non-clear-cell population.
- Disease control rate: 100% at 6.4 mg/kg and 92% at 9.6 mg/kg, with 96% overall in non-clear-cell ovarian cancer.
- All histologies: Including clear cell carcinoma, the overall ORR was 53%, confirmed ORR was 44%, and disease control rate was 95%.
- Response durability: Median duration of response had not been reached at the data cutoff.
- Treatment exposure: Overall, 58% of patients remained on treatment.
- Safety: The most common treatment-emergent adverse events included nausea, neutropenia, and anemia.
- Grade ≥3 neutropenia occurred in 8% and 23% of patients at 6.4 mg/kg and 9.6 mg/kg, respectively.
- Other grade ≥3 events: Anemia occurred in 8% and 14%, while pleural effusion occurred in 5% and 9% of patients at the respective dose levels.
Conclusion
The ZWI-ZW191-101 findings demonstrated promising preliminary antitumor activity with ZW191 in heavily pretreated platinum-resistant ovarian cancer.
The 58% objective response rate and 48% confirmed response rate in the non-clear-cell population support further investigation of FRα-targeted ADC therapy in this setting.
Although both doses demonstrated antitumor activity, the higher incidence of grade ≥3 neutropenia and anemia at 9.6 mg/kg highlights the importance of dose optimization.
Longer follow-up is needed to establish response durability, progression-free survival outcomes, and the potential relationship between FRα expression and treatment benefit. These findings will help guide dose selection for further clinical development.
Source: ESMO Congress 2026, Abstract LBA40; ZWI-ZW191-101 (NCT06555744).
