Ovarian cancer is a lethal disease with an estimated 310,000 new cases and 200,000 deaths experienced worldwide in 2020. The purpose of this study is to assess the adverse events and change in disease activity of mirvetuximab soravtansine with carboplatin, or bevacizumab (Bev), or bev alone in participants with ovarian cancer (OC). Participants must have confirmation of folate receptor alpha (FRa) positivity by the Ventana folate receptor 1 (FOLR1) Assay.
Mirvetuximab Soravtansine (MIRV) is an investigational drug for the treatment of OC. Participants will be assigned to 1 of 3 substudies and further into groups called treatment arms. In substudy 1, arms A-C, participants will receive 1 of 2 doses of MIRV with Bev, or Bev alone. In substudy 2, arms D and E, participants will receive 1 of 2 doses of MIRV with carboplatin, followed by MIRV alone. In substudy 3, arms F and G, participants will receive one of two doses of MIRV with BEV and carboplatin, followed by MIRV with BEV. Approximately 400 participants will be enrolled in the study at 100 sites around the world.
Participants will receive intravenously (IV) infused MIRV with IV infused carboplatin, or IV infused Bev, or IV infused carboplatin and Bev, or IV infused Bev alone. The total study duration will be approximately 40 months.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.
Participants must be willing to provide an archival tumor tissue block or slides or must undergo a procedure to obtain a new tumor biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα expression as defined by the central VENTANA FOLR1 (FOLR1-2.1) assay. Tumors must have FRα-expression in >= 50% of viable tumor cells with >= 2+ staining intensity.
Participants must have an Eastern Cooperative Oncology Group performance status of 0 or 1.
1L participants must have a confirmed diagnosis of Federation of Gynecology and Obstetrics (FIGO) Stage III or IV high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer.
Participant has a local homologous recombination deficient (HRD) or breast cancer susceptibility gene (BRCA) test result available. Participants with BRCA wild-type will need to have a local HRD test result available.
Participants with progressive disease (PD) while on triplet therapy or after the first day of their last triplet therapy cycle and before randomization.
Participants who receive an intervening dose of bevacizumab after the first day of their last triplet therapy cycle and before randomization.
Participants who received prior treatment with mirvetuximab soravtansine (MIRV), any FRα-targeting agent, or Poly(ADP-ribose) polymerase inhibitor (PARPi).
Neoadjuvant +/- adjuvant therapies are considered 1 line of therapy if the neoadjuvant and adjuvant correspond to 1 fully predefined regimen; otherwise, they are counted as 2 prior regimens.
Parallel
Mirvetuximab Soravtansine
DrugIntravenous (IV) infusion
Bevacizumab
DrugIV Infusion
Carboplatin
DrugIV Infusion
7
Treatment groupsSee each treatment group below.
Substudy 1, 2, and 3: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) (any grade, Grade >= 3)
TEAEs defined as any adverse event (AE) with the onset after the first dose of study drug until 30 days after the last dose of the study drug.
Substudy 1, 2, and 3: Number of Participants with TEAEs Leading to Discontinuation
TEAEs defined as any adverse event (AE) with the onset after the first dose of study drug until 30 days after the last dose of the study drug.
Substudy 1, 2, and 3: Number of Participants with Ocular Adverse Events (AEs) (any grade, Grade >= 2)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Substudy 1, 2, and 3: Overall Response (OR) as Assessed by the Investigator per RECIST v1.1
OR is defined as achieving a best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Substudy 1, 2, and 3: CA-125 Response per Gynecologic Cancer Intergroup (GCIG) Criteria
CA-125 response per GCIG Criteria.
Substudy 1, 2, and 3: Duration of Response (DOR) as Assessed by the Investigator per RECIST v1.1
DoR is defined for confirmed responders as the time from the participants' initial response (CR or PR) to the first occurrence of radiographic progression per RECIST v1.1 or death from any cause.
Substudy 1, 2, and 3: Number of Participants with Peripheral Neuropathy AEs (any grade, Grade ≥ 2)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Substudy 1, 2, and 3: Number of Participants with Adjudicated Pneumonitis/ Interstitial Lung Disease (ILD) (any grade)
ILD is defined by ILD standardized MedDRA query (SMQ) (broad) per investigator and determined per adjudication.
