Phase III Study of AZD5335 Versus Mirvetuximab Soravtansine or Investigator's Choice Chemotherapy in Patients with FRα-High or FRα-Low Platinum-Resistant Epithelial Ovarian Cancer

The primary objective is to evaluate the efficacy of AZD5335 in patients with platinum-resistant ovarian cancer. In the FRα-high cohort, efficacy is assessed by comparing AZD5335 to mirvetuximab soravtansine using progression-free survival. In the FRα-low cohort, efficacy is evaluated by comparing AZD5335 to investigator’s choice chemotherapy based on progression-free survival. The secondary objectives include the assessment of overall survival for both the FRα-high and FRα-low cohorts.

This clinical trial involves 791 female participants diagnosed with platinum-resistant epithelial ovarian cancer. The study population includes individuals with high-grade serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer. Eligible participants must demonstrate platinum resistance based on specific progression timelines following prior platinum-based therapy. The cohort is categorized by FRα expression levels to evaluate efficacy through progression-free survival. Participants must have received between one and three prior systemic lines of anti-cancer therapy and must provide a formalin-fixed paraffin-embedded tumor tissue sample. In cases of documented BRCA mutation, prior treatment with poly ADP ribose polymerase inhibitors is required if clinically indicated and tolerated. The population is identified as vulnerable.

This Phase III, randomised, open-label study evaluates the efficacy of AZD5335 in patients with platinum-resistant epithelial ovarian cancer. The research is divided into two cohorts based on folate receptor alpha (FRα) expression levels. In the high FRα cohort, AZD5335 is compared against mirvetuximab soravtansine. In the low FRα cohort, AZD5335 is compared against investigator's choice chemotherapy, which may include doxorubicin hydrochloride, liposomal, paclitaxel, or topotecan. The primary endpoint is progression-free survival (PFS), while the secondary endpoint is overall survival (OS). The trial is estimated to occur between April 2026 and May 2030.

The experimental treatment consists of AZD5335 administered as a solution for infusion via intravenous infusion.

The comparator mirvetuximab soravtansine is administered via intravenous infusion at a dosage of 6 mg/kg.

Investigator's choice chemotherapy includes doxorubicin hydrochloride, liposomal administered via intravenous infusion at a dose of 40 mg/m², paclitaxel administered via intravenous infusion at a dose of 80 mg/m², or topotecan administered via intravenous infusion at a dose of 4 mg/m².

The efficacy of AZD5335 will be evaluated based on specific primary and secondary endpoints in patients with platinum-resistant epithelial ovarian cancer. The primary endpoint is progression-free survival (PFS), which is defined as the interval from randomization to radiographic progression or death from any cause. Radiographic progression will be assessed by the investigator according to RECIST v1.1 criteria.

Secondary efficacy assessment includes overall survival (OS), defined as the time from randomization until death from any cause.