Randomized dose optimization of ZW191 in heavily pretreated patients with platinum-resistant ovarian cancer (PROC)

ZWI-ZW191-101

Patient / Population Intervention / Exposure Comparison Outcome

In heavily pretreated patients with platinum-resistant ovarian cancer, the folate receptor α-targeting antibody-drug conjugate ZW191 produced objective responses in 58% of response-evaluable patients without clear cell carcinoma at both doses tested.

N

65patients

Design

First-in-human study (NCT06555744) in which Part 2 randomised adults with platinum-resistant ovarian cancer who had progressed on available systemic therapies 1:1 to two intravenous doses of ZW191, a folate receptor α (FRα)-targeting antibody-drug conjugate, given every 3 weeks, regardless of histology, FRα expression or number of prior lines; blinding not stated.

Endpoint

Primary objectives were safety, tolerability and antitumour activity.

ResultIn response-evaluable patients excluding clear cell carcinoma, objective response rate was 58% with the lower dose vs 58% with the higher dose (58% overall, n=69), confirmed ORR 52% vs 45% (48% overall) and disease control rate 100% vs 92% (96% overall). Including clear cell carcinoma, ORR was 53% vs 52% (53% overall, n=78), confirmed ORR 47% vs 41% (44% overall) and DCR 97% vs 93% (95% overall). Median duration of response was not reached. The most common treatment-emergent adverse events were nausea (32% vs 60%), neutropenia (19% vs 42%) and anaemia (27% vs 26%). Grade ≥3 events were neutropenia (8% vs 23%), anaemia (8% vs 14%) and pleural effusion (5% vs 9%). 58% of patients remained on treatment.

Lee J, Sommerhalder D, Fidalgo JAP, et al. Presented at ESMO Congress 2026, abstract LBA40, 24 October. Not yet published.

Discussion & critique

In heavily pretreated patients with a median of 4 prior lines, the abstract reports high and similar response rates at both doses, with more nausea and neutropenia at the higher dose. The dose groups pool the 15 non-randomised Part 1 patients with the 65 randomised in Part 2, and there is no control arm, so the results cannot show how ZW191 compares with standard treatment. Median follow-up was only 5 months, median duration of response was not reached and progression-free survival is not reported, so whether responses last is still unknown. The abstract does not report efficacy by FRα expression, and response rates are based only on patients with at least one post-baseline scan.