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

NCT04606914 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IRB-300005764
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Ovarian Cancer; Fallopian Tube; Primary Peritoneal Cancer

Keywords

First line treatment; Advanced epithelial ovarian cancer; mirvetuximab soravtansine; IMGN853

Outcome Measures

Primary Outcomes (3)

• 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.

  Baseline through 2 years

• Objective response rate (ORR)

  To assess ORR per iRECIST 1.1 and GCIG CA-125 criteria

  Baseline through 2 years

• Radiographic tumor assessment per RECIST v1.1 criteria

  Radiographic tumor response by CT or MRI of chest, abdomen, and pelvis using RECIST v1.1

  Baseline through 2 years

Secondary Outcomes (2)

• Serum Cancer Antigen 125 (CA-125) assessments

  Baseline through 2 years

• Safety profile of treatment with carboplatin-mirvetuximab soravtansine according to CTCAE v4.03

  Baseline through 2 years

Study Arms (2)

Arm A: alpha receptor positive_neoadjuvant chemotherapy regimen

EXPERIMENTAL

* IV Carboplatin AUC 5 (Q21 days) 7 cycles (first cycle is Carbo alone, dosing for C1D1 will be provider's choice) * IV Mirvetuximab 6 mg/kg (adjusted ideal body weight) day 1 (Q21 days) 6 cycles (starting with cycle #2)

Drug: mirvetuximab soravtansine (MIRV; IMGN853)

Arm B: alpha receptor negative

NO INTERVENTION

If a patient is found to be negative for FRα expression, they will be ineligible to receive the study treatment under the main study (Arm A). FRα negative patients will be enrolled under the biomarker-only arm (Arm B), and their treating physician can select the treatment they deem appropriate.

Interventions

mirvetuximab soravtansine (MIRV; IMGN853) DRUG

Mirvetuximab 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.

Arm A: alpha receptor positive_neoadjuvant chemotherapy regimen

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Women with biopsy-confirmed high grade serous epithelial ovarian cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (9)

University of Alabama at Birmingham Womens & Infants Center

Birmingham, Alabama, 35233, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94158, United States

RECRUITING

University of Minnesota - Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

University of Mississippi Medical Center

Oxford, Mississippi, 36607, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43026, United States

RECRUITING

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Allegheny Health Network

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

University of Virginia

Richmond, Virginia, 23219, United States

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

mirvetuximab soravtansine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Rebecca Arend, M.D.

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca Arend, M.D.

CONTACT

205-934-4986; rarend@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 16, 2020
• First Posted: October 28, 2020
• Study Start: May 27, 2021
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2028
• Last Updated: September 8, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)