This Phase 3 study is designed to compare the efficacy and safety of mirvetuximab soravtansine (MIRV) vs. IC chemotherapy in participants with platinum-resistant high-grade epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of FRα. Participants will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. The FRα positivity will be defined by the Ventana FOLR1 (FOLR1-2.1) CDx assay.
Participants will be randomized to either MIRV or IC chemotherapy (paclitaxel, PEGylated liposomal doxorubicin, or topotecan).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
453
Mirvetuximab Soravtansine will be administered per dose and schedule specified in the arm.
Paclitaxel will be administered per dose and schedule specified in the arm.
Topotecan will be administered per dose and schedule specified in the arm.
Pegylated liposomal doxorubicin will be administered per dose and schedule specified in the arm.
University of Alabama at Birmingham (UAB) GYN Oncology
Birmingham, Alabama, United States
Alaska Women's Cancer Care
Anchorage, Alaska, United States
Arizona Oncology Associates, PC - HAL - USOR
Phoenix, Arizona, United States
Mayo Clinic
Phoenix, Arizona, United States
USOR: Arizona Oncology Associates, PC - HOPE
Tucson, Arizona, United States
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
PFS was defined as the time from randomization until progressive disease (PD) or death whichever occurred first. PD: At least a 20% increase in the sum of the longest diameters (SoD) of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 millimeters (mm). Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Time frame: From randomization until PD or death, whichever occurred first (up to approximately 36 months)
Objective Response Rate (ORR), as Assessed by the Investigator Using RECIST v1.1
ORR was defined as percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least 30% decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD.
Time frame: Up to approximately 36 months
Overall Survival Assessed by the Investigator Using RECIST v1.1
Overall survival was defined as the time from the date of first dose until the date of death from any cause, estimated using the Kaplan-Meier method.
Time frame: Up to approximately 45 months
Number of Participants Achieving at Least 15 Point Absolute Improvement in the Abdominal/Gastrointestinal (GI) Scale of European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Ovarian Cancer Module 28 (QLQ-OV28)
The EORTC QLQ-OV28 is specific for ovarian cancer and consists of 28 items assessing abdominal/gastrointestinal symptoms (6 items), peripheral neuropathy (2 items), other chemotherapy side effects (5 items), hormonal symptoms (2 items), body image (2 items), attitudes to disease/treatment (3 items), sexuality (4 items) and 4 other single items. Each scale was scored from 0 to 100 with higher scores on the symptom scales indicating greater symptom burden. Higher scores represent a higher ("better") level of functioning. Presented here are the number of participants achieving at least 15 point absolute improvement at Week 8 or Week 9 in the abdominal/GI scale of the EORTC QLQ-OV28.
Time frame: Baseline and Week 8 or 9
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence that developed or worsened in severity during the conduct of a clinical study and did not necessarily have a causal relationship to study drug. TEAEs were defined as AEs with an onset date on or after the first dose of study drug, and within 30 days of the last dose of study drug or prior to the start of a new anticancer treatment, whichever occurred first. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time frame: Up to approximately 37 months
Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1
DOR was defined as the time from the date of the first response (CR or PR), until the date of PD or death from any cause, whichever occurred first. DOR for participants who have not progressed or died at the time of analysis are censored at the date of their last tumor assessment. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also have demonstrated an absolute increase of at least 5 mm. DOR was estimated using the Kaplan-Meier method.
Time frame: Up to approximately 34 months
Percentage of Participants With Cancer Antigen 125 (CA-125) Confirmed Clinical Response Per Gynecologic Cancer Intergroup (GCIG) Criteria
The GCIG CA-125 response was defined as at least 50% reduction in CA-125 levels from baseline. The response must have been confirmed and maintained for at least 28 days.
Time frame: Baseline up to approximately 36 months
Time to Second Progression-Free Survival (PFS 2)
PFS 2 was defined as the time from date of randomization until second disease progression or death whichever occurred first.
Time frame: Up to approximately 44 months
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University of Arizona Cancer Center
Tucson, Arizona, United States
UCLA - JCCC Dept of OBGYN - Women's Health Clinical Research Unit
Los Angeles, California, United States
Hoag Cancer Center
Newport Beach, California, United States
University of California San Francisco
San Francisco, California, United States
Olive View - UCLA Medical Center
Sylmar, California, United States
...and 204 more locations