Torvutatug Samrotecan Plus Bevacizumab as First-line Maintenance in Homologous Recombination Deficiency (HRD) Negative Advanced Epithelial Ovarian Cancer

This study aims to see if torvu-sam in combination with bevacizumab allows patients to live longer without the cancer getting worse, compared to patients receiving bevacizumab.

Eligible patients will be those patients who have not progressed following completion of first line induction treatment with Platinum-based chemotherapy (PBC) and bevacizumab. All patients must be HRD-negative through pre-existing study approved local test or prospective central test and have a confirmed folate receptor alpha status determined by prospective central test.

• Torvutatug samrotecan (Drug), also known as AZD5335, Torvu-sam: Antibody drug conjugate
• Bevacizumab (Drug), also known as Antiangiogenic therapy: Monoclonal antibody inhibitor of Vascular Endothelial Growth Factor

Primary outcomes

• Progression Free Survival (PFS) [up to approximately 5 years]: PFS is defined as the time from randomization to radiographic progression as assessed by BICR per RECIST v1.1, or death due to any cause.

Secondary outcomes

• Overall Survival (OS) [up to approximately 7 years]: OS is defined as the time from randomization until the date of death due to any cause.
• Second progression free survival (PFS2) [up to approximately 5 years]: PFS2 is defined as time from randomisation to the earliest of the progression event (following the initial investigator-assessed progression) after first subsequent therapy, or death.
• Time to First Subsequent Therapy (TFST) [up to approximately 7 years]: TFST is defined as time from randomisation until the start date of the first subsequent anti-cancer therapy after discontinuation of randomised treatment, or death due to any cause.
• Time to Second Subsequent Therapy (TSST) [up to approximately 7 years]: TSST is defined as time from randomisation until the start date of the second subsequent anti-cancer therapy after discontinuation of randomised treatment, or death due to any cause.
• Health-related Quality of Life (HrQoL) [up to approximately 5 years]: Change from baseline and time to deterioration in global health status/quality of life (GHS/QoL), physical functioning (PF), and ovarian cancer symptoms (EORTC IL433).
• Number and percentage of participants with adverse events as graded by CTCAE v6 criteria [up to approximately 7 years]: Adverse Event Incidence

Sex: Female, ages: 18 Years to any

Key Inclusion Criteria:

* Participants with newly diagnosed FIGO Stage III/IV, histologically confirmed epithelial high-grade ovarian, fallopian tube or primary peritoneal carcinoma
* Provision of an archival FFPE tumour sample
* Participants who have completed at least 6 cycles and a maximum of 8 cycles of first-line Platinum-based chemotherapy (PBC) prior to randomisation
* Participants must have received a minimum of 3 cycles of bevacizumab in combination with the 3 last cycles of PBC, prior to randomisation
* Participants who have completed cytoreductive surgery or have inoperable disease
* Participants with non-progressive disease upon completion of front-line induction therapy
* HRD negative tumour

Key Exclusion Criteria:

* Participants with tumours of non-epithelial origin, borderline tumours, or low-grade epithelial tumours.
* Participants with history of (non-infectious) ILD/pneumonitis that required steroids or supplemental oxygen, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening
* Participants with non-healing wound, active ulcer, or bone fracture
* Participants with evidence of active or ongoing bowel obstruction
* Prior exposure to any FRα-targeted therapy, including MIRV, or any TOP1i Antibody-drug Conjugate (ADC)

86 more sites not listed.