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

Summary

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.

Eligibility

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:
* History of hepatitis B or C infection (whether or not on active antiviral therapy)
* History of human immunodeficiency virus (HIV) infection
* Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to the first dose of MIRV
* Patients with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
* Patients with clinically significant cardiac disease including, but not limited to, any of the following:
* Myocardial infarction ≤ 6 months prior to first dose
* Unstable angina pectoris
* Uncontrolled congestive heart failure (New York Heart Association \> class II)
* Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
* Uncontrolled cardiac arrhythmias
* Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment
* Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
* Patients with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
* Patients requiring use of folate-containing supplements (eg, folate deficiency)
* Patients with prior hypersensitivity to monoclonal antibodies (mAb)
* Women who are pregnant or breastfeeding
* Patients who received prior treatment with MIRV or other FRα-targeting agents
* Patients with untreated or symptomatic central nervous system (CNS) metastases
* Patients with a history of other malignancy within 3 years prior to enrollment Note: patients with tumors with a negligible risk for metastasis or death (eg, adequately controlled basal-cell carcinoma or squamous-cell carcinoma of the skin, or carcinoma in situ of the cervix or breast) are eligible

Conditions4

Interventions1

Locations9 sites

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