FDA Grants Fast Track Designation to FRα-Targeting ADC for Ovarian Cancer

The FDA has granted fast track designation to ZW191, an antibody-drug conjugate (ADC) targeting folate receptor-α (FRα), for the treatment of patients with advanced or metastatic platinum-resistant ovarian cancer, according to Zymeworks, the biotechnology company developing the agent.¹

ZW191 is engineered to bind to FRα, a cell-surface protein with high expression across several tumor types. According to Zymeworks, FRα is expressed in approximately 75% of high-grade serous ovarian carcinomas, more than 50% of endometrial cancers, and roughly 70% of lung adenocarcinomas.¹ The Fast Track Designation will accelerate the development and review of ZW191 in ovarian cancer.

"Receiving Fast Track Designation for ZW191 highlights the potential of this program to address significant unmet medical needs for patients with previously treated advanced ovarian cancer," Sabeen Mekan, MD, Senior Vice President and Chief Medical Officer at Zymeworks, stated in a news release. "The designation was granted irrespective of FRα expression, highlighting ZW191's potential of extending treatment benefits to a broad group of patients without need for biomarker selection."

Ongoing Phase 1 Trial

ZW191 is currently under evaluation in a phase 1, first-in-human study (NCT06555744) enrolling patients with advanced solid tumors.² The trial is designed to assess safety, tolerability, pharmacokinetics, and preliminary antitumor activity, with findings intended to inform the compound's future development strategy, including optimal dosing and patient selection criteria.

Patient eligibility criteria for the trial include the following: pathologically or cytologically confirmed diagnosis of locally advanced, recurrent, or metastatic solid tumors; measurable disease (RECIST v1.1); and an ECOG performance status of 0 or 1. Patients are not eligible to enroll if they had prior treatment with any topoisomerase 1 inhibitor–based ADC; have known additional malignancy that is progressing or requires active treatment; or have acute or chronic uncontrolled renal disease, pancreatitis, or liver disease.²

Initial data from the trial were reported during a poster presentation at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.³ The results shared were for a population of 41patients with heavily pretreated platinum-resistant ovarian cancer, metastatic endometrial cancer, and metastatic NSCLC who were enrolled regardless of FRα expression levels. The patients were treated at doses of 1.6 to 11.2 mg/kg of ZW191.

Across all response-evaluable patients, the objective response rate (ORR) at the initial analysis was 44%. Notably, in patients with gynecological cancers treated at of doses 6.4 mg/kg or higher, the ORR was 64%. Responses were observed at all doses evaluated at 3.2 mg/kg and above.³

ZW191 had a manageable safety profile, with low rates of high-grade adverse events and no serious treatment-related events or discontinuations. Anemia, occurring in 10% of patients, was the most common grade 3 or higher treatment-related adverse event, followed by neutropenia and thrombocytopenia, each occurring in 5% of patients. Dose reductions and delays were infrequent, according to study investigators.

The maximum-tolerated dose of ZW191 was identified to be 11.2 mg/kg. Two doses were selected for dose optimization, being 6.4 and 9.6 mg/kg, with 30 patient cohorts planned for each.

Context Within the FRα-Targeting ADC Field

FRα is considered an attractive candidate for molecularly targeted approaches in ovarian cancer given its near-ubiquitous expression on the surface of ovarian cancer cells and its capacity to internalize large molecules containing a cytotoxic payload. Several FRα-targeting ADCs have entered clinical development in recent years, reflecting increasing interest in this receptor as a therapeutic target in gynecologic malignancies.

REFERENCES

1. Zymeworks receives U.S. FDA Fast Track designation for ZW191, an FRα-targeting antibody-drug conjugate. News release. Yahoo Finance. March 30, 2026. Accessed March 30, 2026. https://tinyurl.com/ahms5d92

2. A study of ZW191 in participants with solid tumors. ClinicalTrials.gov. Updated March 6, 2026. Accessed March 30, 2026. https://tinyurl.com/ym49586a

3. Zymeworks presents initial clinical data from the phase 1 trial of ZW191, an antibody-drug conjugate targeting folate receptor-α at AACR-NCI-EORTC conference. News release. Zymeworks Inc. October 23, 2025. Accessed March 30, 2026. https://tinyurl.com/5x5v4vyh