Epithelial Ovarian Cancer
Conditions
Keywords
Epithelial Ovarian Cancer, Peritoneal Cancer, Follopian Tube Cancer, Platinum Resistant Ovarian Cancer
Brief summary
The intention of the study is to demonstrate superiority of AZD5335 versus standard of care by assessment of progression-free survival (PFS) in women with high-grade, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, expressing high or low FRα levels.
Detailed description
Approximately 1100 adult participants will be enrolled after central FRα testing into two independent cohorts (about 550 FRα-high and 550 FRα-low) and randomized 1:1 within each cohort to receive AZD5335 or the relevant standard of care (mirvetuximab soravtansine in FRα-high; investigator's choice single-agent chemotherapy in FRα-low). Participants will remain on assigned treatment and undergo regular tumor evaluations per RECIST v1.1 until disease progression or another reason for treatment discontinuation. All participants will be followed for overall survival. An independent data monitoring committee (IDMC) of external experts will periodically review unblinded safety and interim efficacy to confirm participant safety and study integrity.
Interventions
DRUGAZD5335
antibody drug conjugate
DRUGMirvetuximab Soravtansine (MIRV)
antibody drug conjugate
DRUGPaclitaxel
chemotherapy
DRUGPegylated liposomal Doxorubicin (PLD)
chemotherapy
DRUGTopotecan
chemotherapy
Sponsors
European Network of Gynecological Oncological Trial Groups (ENGOT)
GOG Foundation, Inc. (GOG Foundation)
Ventana Medical Systems, Inc
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free Survival (PFS) | Up to approximately 5 years | PFS is defined as the time from randomization to radiographic progression as assessed by the Investigator per RECIST v1.1, or death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to approximately 5 years | OS is defined as the time from randomisation until the date of death due to any cause. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DoR) | Up to approximately 5 years | DoR is defined as the time from the date of first documented response until the date of documented progression per RECIST v1.1, as assessed by the investigator, or death due to any cause. |
| Second progression free survival (PFS2) | Up to approximately 5 years | Time from randomization to second progression or death (PFS2) is defined as the time from randomization to the earliest progression event (following the initial progression) subsequent to the first subsequent therapy, or death. |
| CA-125 Response Rate (CA-125 RR) | Up to approximately 5 years | Proportion of participants achieving CA-125 response per GCIG criteria |
| Health-related Quality of Life (HrQoL) | Up to approximately 5 years | Change from baseline in selected subscales of EORTC QLQ C30; global health status, physical function and EORTC QLQ OV28 hormonal symptoms (EORTC IL). |
| Objective response date (ORR) | Up to approximately 5 years | ORR is defined as the proportion of participants who have a complete or partial response, as determined by the investigator, per RECIST v1.1. |
Countries
Australia, Belgium, Brazil, Canada, Chile, China, Czechia, Denmark, France, Germany, Greece, India, Ireland, Israel, Italy, Japan, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Primary ContactAstraZeneca Clinical Study Information Center
Outcome results
None listed