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.
Patients who have previously been treated with a systemic anti-cancer therapy
Patients with low-grade serous, endometrioid, clear cell, or mucinous histology
Patients with active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, wet age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy with macular edema, macular degeneration, presence of papilledema, and /or monocular vision
History of hepatitis B or C infection (whether or not on active antiviral therapy)
Single group
mirvetuximab soravtansine (MIRV; IMGN853)
DrugMirvetuximab soravtansine (also known as IMGN853 and MIRV) is an antibody-drug conjugate (ADC) that consists of a high affinity humanized monoclonal antibody against folate receptor α (FRα, the protein product of the folate receptor 1 \[FOLR1\] gene) that is conjugated to a cytotoxic maytansinoid by the hindered disulfide succinimidyl 4-(pyridin-2-yl)disulfanyl)-2-sulfo-butyrate linker (sulfo-SPDB) linker. FRα is a glycosyl-phosphatidylinositol (GPI)-linked protein, which shows limited normal tissue expression and high expression on the surface of solid tumors, particularly epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (referenced herein collectively as EOC), endometrial cancer, non-small cell lung cancer (NSCLC), and renal cell cancer.
progression free survival (PFS)
To assess percentage of patients with advanced-stage ovarian, fallopian tube, and peritoneal cancers per Response Evaluation Criteria in Solid Tumors (RECIST)1.1 and Gynecological Cancer Intergroup Cancer antigen 125 (GCIG CA-125) criteria.
Objective response rate (ORR)
To assess ORR per iRECIST 1.1 and GCIG CA-125 criteria
Radiographic tumor assessment per RECIST v1.1 criteria
Radiographic tumor response by CT or MRI of chest, abdomen, and pelvis using RECIST v1.1
Serum Cancer Antigen 125 (CA-125) assessments
Serum CA-125 will be assessed by the same laboratory throughout the study.
Safety profile of treatment with carboplatin-mirvetuximab soravtansine according to CTCAE v4.03
To determine the nature and degree of toxicity oftreatment with carboplatin-mirvetuximab soravtansine according to Common Terminology Criteria for Adverse Events (CTCAE) v4.03
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University of Alabama at Birmingham
Lead sponsor
AbbVie
Collaborator
