Zymeworks ZW191 posts 78.6% response rate in FRα-positive ovarian cancer
Zymeworks has presented Phase 1 data for ZW191, its folate receptor alpha-targeting antibody-drug conjugate, at the ESMO Gynaecological Cancers Congress 2026, reporting a confirmed objective response rate of 78.6% in FRα-positive platinum-resistant ovarian cancer patients and 47.4% in those classified as FRα-negative, across all dose levels studied.
The results, drawn from Part 1 of the ongoing Phase 1 study with a data cutoff of 9 March 2026, also showed a confirmed ORR of 58.8% across the overall platinum-resistant ovarian cancer population and 65.2% in the 6.4–9.6 mg/kg dose range. Disease control rates reached 100% in FRα-positive patients and 89.5% in the FRα-negative group. Median duration of response had not been reached at the data cutoff, and median progression-free survival was 7.6 months across ovarian and endometrial cancer cohorts combined.
Clinical significance
The activity seen in FRα-negative patients is a particular point of interest. Existing approved therapies in the FRα space, notably mirvetuximab soravtansine, are indicated for patients with high FRα expression, leaving a substantial proportion of ovarian cancer patients without an approved targeted option. ZW191's design incorporates a novel proprietary payload, ZD06519, a topoisomerase-1 inhibitor capable of bystander killing of adjacent tumour cells, which the company says may account for the activity observed regardless of receptor expression.
Sabeen Mekan, Chief Medical Officer at Zymeworks, said the response rate in FRα-positive patients "compares favourably with currently available therapies, while maintaining meaningful activity in patients with negative FRα expression." Presenting author Kosei Hasegawa of Saitama Medical University International Medical Center noted that the data suggest ZW191 "could expand the benefit of FRα-targeted therapy to a broader patient population."
On safety, treatment-emergent adverse events occurred in 98% of patients, with grade 3 or higher events reported in 55%. The most common high-grade toxicities were neutropenia at 24%, anaemia at 20%, and thrombocytopenia at 12%. Serious adverse events were recorded in 35% of patients, and 20% discontinued due to adverse events. Zymeworks characterised the overall profile as manageable and consistent with continued development.
Competitive landscape and next steps
The FRα-targeted ADC space has become notably competitive. ImmunoGen's mirvetuximab soravtansine received FDA accelerated approval in 2022 and full approval in 2024 for FRα-positive ovarian cancer, establishing a commercial benchmark. Several other ADC programmes, including those from AbbVie and Sutro Biopharma, are in earlier clinical development targeting the same receptor. The differentiation thesis for ZW191 rests on its broader activity profile across expression levels and its novel payload, claims that will require confirmation in larger, randomised cohorts.
Part 2a of the Phase 1 study, a dose optimisation cohort of approximately 60 platinum-resistant ovarian cancer patients randomised to 6.4 mg/kg or 9.6 mg/kg every three weeks, has now completed enrolment. Data from that portion are expected to inform dose selection ahead of any potential pivotal programme and will be presented at a future medical meeting. Zymeworks said the broad therapeutic window identified in dose escalation supports continued clinical development, but did not indicate a timeline for a Phase 2 or pivotal study initiation.
Gynaecologic cancers remain an area of significant commercial and scientific interest, with platinum resistance in ovarian cancer representing one of the most difficult-to-treat subgroups in oncology. An ADC that demonstrably retains activity below conventional FRα expression thresholds would represent a meaningful clinical advance, though investors and oncologists will look to the Part 2a readout for the controlled, randomised data needed to substantiate that position.