Single-Arm Phase II Study of Carboplatin and Mirvetuximab Soravtansine in First-Line Treatment of Patients Receiving Neoadjuvant Chemotherapy With Advanced-Stage Ovarian, Fallopian Tube or Primary Peritoneal Cancer Who Are Folate Receptor α Positive
The proposed study design is a single arm Phase II trial to document the feasibility of carboplatin-mirvetuximab - in patients with advanced-stage EOC. Patients with biopsy confirmed, newly diagnosed, advanced-stage serous EOC deemed appropriate for NACT will have their tumors evaluated for FRα receptor over-expression via a centralized immunohistochemical assay (IHC) and identified as appropriate for study participation if IHC staining is PS2+ in \>75% of cells (40% of all serous patients). Eligible patients will receive NACT with one cycle of carboplatin, followed by mirvetuximab + carboplatin (if FRα +) every 21 days for three cycles prior to interval cytoreductive surgery (iCRS). A total of 70 will be included in the study. Following completion of 4 cycles total of NACT and after allowing for appropriate recovery of cycle # 4, patients eligible for surgery, will undergo an iCRS. Patients will then complete 3 more cycles of mirvetuximab + carboplatin for a total of 7 intended cycles of treatment. It is up to the treating physician if they want to add bevacizumab to the last 2 cycles or use any type of maintenance therapy. The decision to add bevacizumab or use maintenance therapy does not need to be made upfront. Patients will sign a screening consent form prior to tissue biopsy. If a patient is found to be FRα negative, their treating physician can select the treatment they deem appropriate and the patient will be declared a screen failure. Patients with BRCA mutations are not excluded from this trial and are allowed to receive standard of care maintenance therapy including bevacizumab and/or PARP inhibitors.
• Patients must have biopsy-confirmed high grade serous epithelial ovarian cancer.
• Patients must present with stage III or IV disease and be appropriate to receive neoadjuvant chemotherapy
• Patients must be willing to provide an archival tumor tissue block or slides, or undergo procedure to obtain a new biopsy using a low-risk, medically routine procedure for immunohistochemistry (IHC) confirmation of FRα positivity
• Patients must have a performance status of 0 or 1.
• Patient's tumor must be positive for FRα expression as defined by a score of PS2+ intensity in \>75% of cells
• Patients must have adequate hematologic, liver and kidney functions defined as:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1,500/μL)
• Platelet count ≥ 100 x 109/L (100,000/μL) without platelet transfusion in the prior 10 days
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
• Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin \< 3.0 x ULN)
• Serum albumin ≥ 2 g/dL
• Patients must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements
• Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) (as defined in Section 5.8.6 while on MIRV and for at least 4 months after the last dose
• WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV