A Randomised, Open-label, Phase III Study of AZD5335 Versus Mirvetuximab Soravtansine in FRα-high and AZD5335 Versus Investigator's Choice Chemotherapy in FRα-low Expressing High-grade Platinum-resistant Epithelial Ovarian Cancer Patients (TREVI-OC-01)

Key Inclusion criteria

• Participants with confirmed diagnosis of high-grade serous EOC, primary peritoneal cancer, or fallopian tube cancer.
• Participants must have platinum-resistant disease:
• Participants who have only had one prior line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response (CR or PR) and then progressed between > 3 months and ≤ 6 months after the date of the last dose of platinum.
• Participants who have received 2 or 3 lines of platinum therapy must have progressed ≤ 6 months after the date of the last dose of platinum.
• Participants must have radiologically progressed on or after their most recent line of therapy.
• Participants must have received at least one, but no more than 3, prior systemic lines of anti-cancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment
• Participants with documented BRCA mutation (germline and/or somatic) must have received prior PARPi if the participant is eligible per approved label and standard-of-care institutional guidelines, except in cases of documented contraindication, precaution or intolerance.
• Provision of an FFPE tumour tissue sample

Key Exclusion criteria

• Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumours containing any of the above histologies, or low-grade or borderline ovarian tumour.
• Primary platinum-refractory disease, defined as disease that did not respond to or has progressed ≤ 3 months after the last dose of first line platinum-containing chemotherapy.
• Participants with active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring
• Current signs, symptoms, or clinical investigations consistent with bowel obstruction, including sub-occlusive disease.
• Participant has non-infectious ILD/pneumonitis or has a history of non-infectious ILD/pneumonitis that required oral or IV steroids or supplemental oxygen, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Prior treatment with any FRα-targeted therapy, including MIRV, or any TOP1i ADC.
• Major surgical procedure within 4 weeks of the first dose of study intervention

• Primary
  • PFS
  • OS
• Secondary
  • PFS2
  • ORR
  • DoR
  • QOL
  • CA-125 response rate