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

Description

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.

Conditions

Ovarian Cancer, Fallopian Tube, Primary Peritoneal Cancer

Study Overview

Study Details

Study overview

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.

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

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

Condition
Ovarian Cancer
Intervention / Treatment

-

Contacts and Locations

Birmingham

University of Alabama at Birmingham Womens & Infants Center, Birmingham, Alabama, United States, 35233

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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
  • * 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

Ages Eligible for Study

18 Years to

Sexes Eligible for Study

FEMALE

Accepts Healthy Volunteers

No

Collaborators and Investigators

University of Alabama at Birmingham,

Rebecca Arend, M.D., PRINCIPAL_INVESTIGATOR, University of Alabama at Birmingham

Study Record Dates

2028-05-31