A Study of Mirvetuximab Soravtansine vs. Investigator's Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression (MIRASOL)
Epithelial Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer
About this trial
This is an interventional treatment trial for Epithelial Ovarian Cancer focused on measuring Platinum-resistant, Folate-receptor alpha expression, Phase 3, Antibody-drug conjugate, mirvetuximab soravtansine, IMGN853, Epithelial Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer
Eligibility Criteria
Inclusion Criteria:
- Female patients ≥ 18 years of age
- Patients must have a confirmed diagnosis of high-grade serious epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
Patients must have platinum-resistant disease:
- Patients who have only had 1 line of platinum based therapy must have received at least 4 cycles of platinum, must have had a response (CR or PR) and then progressed between >3 months and ≤ 6 months after the date of the last dose of platinum
- Patients who have received 2 or 3 lines of platinum therapy must have progressed on or within 6 months after the date of the last dose of platinum Note: Progression should be calculated from the date of the last administered dose of platinum therapy to the date of the radiographic imaging showing progression. Note: Patients who are platinum-refractory during front-line treatment are excluded
- Patients must have progressed radiographically on or after their most recent line of therapy
- 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 IHC confirmation of FRα positivity
- Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1 (FOLR-2.1) CDx assay
- Patients must have at least one lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)
Patients must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment:
- Adjuvant ± neoadjuvant considered one line of therapy
- Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as part of the preceding line of therapy (ie, not counted independently)
- Therapy changed due to toxicity in the absence of progression will be considered as part of the same line (ie, not counted independently)
- Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
- Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
Time from prior therapy:
- Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter)
- Focal radiation completed at least 2 weeks prior to first dose of study drug
- Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities
- Major surgery must be completed at least 4 weeks prior to first dose and have recovered or stabilized from the side effects of prior surgery
Patients must have adequate hematologic, liver and kidney functions defined as:
- Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (1,500/μL) without G-CSF in the prior 10 days or long-acting WBC growth factors in the prior 20 days
- Platelet count ≥ 100 x 10^9/L (100,000/μL) without platelet transfusion in the prior 10 days
- Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days
- 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 or their legally authorized representative 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 5.9.6 in the protocol) while on study drug and for at least 3 months after the last dose of MIRV or at least 6 months after the last dose of paclitaxel, pegylated liposomal doxorubicin, or topotecan
- WCBP must have a negative pregnancy test within 4 days prior to the first dose of study drug
Exclusion Criteria:
- Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade or borderline ovarian tumor
- Patients with primary platinum-refractory disease, defined as disease that did not respond to (CR or PR) or has progressed within 3 months of the last dose of first line platinum-containing chemotherapy
- Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow
- Patients with > Grade 1 peripheral neuropathy per CTCAE v5.0
- 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:
- Active hepatitis B or C infection (whether or not on active antiviral therapy)
- HIV infection
- Active cytomegalovirus infection
- Any other concurrent infectious disease requiring IV antibiotics within 2 weeks before starting study drug Note: Testing at screening is not required for the above infections unless clinically indicated
- Patients with history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
Patients with clinically significant cardiac disease including, but not limited to, any one 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 assigned to PLD stratum only: Left ventricular ejection fraction (LVEF) below the institutional limit of normal as measured by echocardiography (ECHO) or multigated acquisition (MUGA) scan
- Patients with a history of hemorrhagic or ischemic stroke within six months prior to randomization
- Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
- Patients with a previous clinical diagnosis of non-infectious interstitial lung disease (ILD), including noninfectious pneumonitis
- Patients with required use of folate-containing supplements (eg, folate deficiency)
- Patients with prior hypersensitivity to monoclonal antibodies
- Women who are pregnant or lactating
- Patients with 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 randomization. Note: does not include 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
- Prior known hypersensitivity reactions to study drugs and/or any of their excipients
- People who are detained through a court or administrative decision, receiving psychiatric care against their will, adults who are the subject of a legal protection order (under tutorship/curatorship), people who are unable to express their consent, and people who are subject to a legal guardianship order
- Simultaneous participation in another research study, in countries or localities where this is the health authority guidance
Sites / Locations
- University of Alabama at Birmingham (UAB) GYN Oncology
- Alaska Women's Cancer Care
- Arizona Oncology Associates, PC - HAL - USOR
- Mayo Clinic
- USOR: Arizona Oncology Associates, PC - HOPE
- University of Arizona Cancer Center
- UCLA - JCCC Dept of OBGYN - Women's Health Clinical Research Unit
- Hoag Cancer Center
- University of California San Francisco
- Olive View - UCLA Medical Center
- Kaiser Permanente Oncology Clinical Trials
- USOR: Rocky Mountain Cancer Centers
- Yale University School of Medicine
- Florida Cancer Specialist South Division
- Mayo Clinic Jacksonville
- Women's Care Florida / Women's Cancer Associates
- Florida Cancer Specialist North Division
- Sarasota Memorial Hospital
- Florida Cancer Specialists
- Florida Cancer Specialist East Division
- Memorial University Medical Center
- Hawaii Pacific Health - Kapiolani Medical Center for Women and Children
- Illinois Cancer Specialists
- University of Chicago
- Dr. Sudarshan K. Sharma, Ltd.
- Community Health Network
- University of Kansas Cancer Center
- St. Elizabeth Healthcare
- Norton Cancer Institute
- Ochnser Medical Center Jefferson
- WK Physicians Network/Gynecologic Oncology Associates
- Holy Cross Hospital
- USOR: Maryland Oncology Hematology, P.A.
- Tufts Medical Center
- Baystate Medical Center
- University of Massachusetts
- St. Joseph Mercy Hospital
- Karmanos Cancer Institute
- Mayo Clinic Rochester
- USOR: Minnesota Oncology Hematology, PA
- HCA Midwest Kansas City/ Sarah Cannon
- Sletten Cancer Institute
- Center of Hope
- The Valley Hospital, Inc
- Holy Name Medical Center
- Columbia University Medical Center
- FirstHealth of the Carolinas Outpatient Cancer Center
- USOR: OHC - Oncology_Hematology Care Clinical Trials, Inc.
- MetroHealth Medical Center
- Cleveland Clinic
- Columbus NCORP
- Zangmeister Cancer Center
- The Ohio State University Wexner Medical Center
- Stephenson Cancer Center
- Oklahoma Cancer Specialists and Research Institute
- USOR: Willamette Valley Cancer Institute and Research Center
- Legacy Gynecologic Oncology
- USOR: Northwest Cancer Specialists, P.C.
- University of Pennsylvania
- Fox Chase Cancer Center
- Magee-Women's Hospital-UPMC
- West Penn Hospital
- Women & Infants Hospital of Rhode Island
- Tennessee Oncology / Sarah Cannon Research Institute
- USOR: Texas Oncology-South Austin
- USOR: Texas Oncology - Fort Worth Cancer Center
- University of Texas, Memorial Hermann
- USOR: Texas Oncology - McAllen South Second
- USOR: Texas Oncology - San Antonio
- USOR: Texas Oncology, P.A.
- USOR: Texas Oncology - The Woodlands, Gynecologic Oncology
- USOR: Texas Oncology - Tyler
- USOR: Texas Oncology, P.A.
- University of Virginia Health System
- USOR: Virginia Cancer Specialists, PC
- Kadlec Clinic Hematology & Oncology
- West Virginia University- MBRCC
- Newcastle Private Hospital
- Prince of Wales Hospital
- Monash Health
- Oncology Clinics Victoria (OCV) - Cabrini Malvern Hospital Location
- Royal North Shore Hospital
- Burnside War Memorial Hospital - The Brian Fricker Oncology Centre
- OLV Ziekenhuis
- AZ Klina
- Universitair Ziekenhuis Antwerpen (UZA) - Borstkliniek
- AZ St-Lucas
- UZ Leuven
- UMHAT Georgi Stranski
- Acibadem City Clinic Tokuda Hospital
- UMHAT "Sv. Ivan Rilski", EAD, Sofia
- Tom Baker Cancer Centre
- Cross Cancer Institute
- The Ottawa Hospital General Campus
- Sunnybrook Health Sciences Center
- Princess Margaret Cancer Centre - University Health Network
- McGill University Health Centre
- Centre Hospitalier de L'Universite de Montreal
- Centre Hospitalier Universitaire de Sherbrooke
- Anhui Provincial Cancer Hospital
- Fujian Cancer Hospital
- Sun Yat-sen University, Cancer Center
- Wuhan Union Hospital of China
- Zhongnan Hospital of Wuhan University
- Hubei Cancer Hospital
- The First Affiliated Hospital of Soochow University
- The First Hospital of Jilin University
- Liaoning Cancer Hospital
- The First Affiliated Hospital of Xi'an Jiaotong University
- Peking University First Hospital
- Beijing Cancer Hospital
- Fudan University Shanghai Cancer Center
- Tianjin Medical University Cancer Institute & Hospital
- Fakultní nemocnice Ostrava
- Všeobecná fakultní nemocnice v Praze
- KNTB a.s. Zlín
- Institut Claudius Regaud
- Centre Oscar Lambret
- Institut de cancérologie de l'ouest, site Angers
- CHRU Besançon
- Institut Bergonie
- Centre Leon Berard
- Institut Paoli Calmettes
- Cochin Hospital
- Groupe Hospitalier Diaconesses Croix Saint-Simon
- Centre Hospitalier Lyon Sud
- Centre Armoricain de radiothérapie, imagerie médicale et oncologie, CARIO
- Institut Curie
- ICO Centre René Gauducheau
- Institut de cancérologie de Lorraine
- Gustave Roussy
- Ulm University Hospital Klinik für Frauenheilkunde und Geburtshilfe
- UMG Göttingen Frauenklinik
- Universitätsklinikum Carl Gustav Carus Dresden
- Universitätsklinikum Bonn
- Städtisches Klinikum Dessau, Zentrum für Klinische Studien
- Klinikum Dortmund gGmbH / Frauenklinik
- University Hospital Freiburg
- Mammazentrum Hamburg am Krankenhaus Jerusalem
- Wolfson Medical Center
- Hadassah Ein Kerem Medical center
- Meir Medical Center
- Sheba Medical Center
- Kaplan Medical Center
- Ziv Medical Center
- IOV Istituto Oncologico
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- ASST Lecco- Ospedale A.Manzoni
- IRCCS - Istituto Europeo di Oncologia (The European Institute of Oncology) (IEO)
- INT Pascale
- Oncologia Azienda Osc-IRCCS Reggio Emilia
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Azienda Ospedaliera Città Della Salute E Della Scienza Di Torino
- Ospedale Mauriziano Umberto I
- National Cancer Center - Center for Uterine Cancer
- Seoul National University Bundang Hospital
- Seoul National University Hospital
- Severance Hospital
- University of Ulsan College of Medicine - Asan Medical Center
- Samsung Medical Center
- Amsterdam UMC
- Maastricht UMC
- Radboud University Medical Center
- Erasmus Medical Center
- Medical University of Gdansk
- Samodzielny publiczny szpital kliniczny nr 1
- Wojewódzki Szpital Specjalistyczny, Oddzial Kliniczny Ginekologii Onkologiczne
- Wielkopolskie Centrum Onkologii
- Szpital Kliniczny im. Ks. Anny Mazowieckiej
- Fundação Champalimaud
- Hospital da Luz, S.A
- Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria
- Hospital Beatriz Angelo
- BIH of Omsk Region "Clinical Oncology Dispensary"
- LLC "VitaMed"
- Leningrad regional oncology dispensa
- State Autonomous Healthcare Institution Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
- Oncology and Radiology Institute Serbia
- Clinical Center Kragujevac
- Oncology Institute Vojvodina, Surgical Oncology Clinic
- Hospital Clínico de Santiago
- H. U. de Jaén
- Hospital Universitario Infanta Sofía
- Institut Català d'Oncologia
- H. San Pedro de Alcántara
- Hospital Provincial de Castellon
- Hospital de San Chinarro-Clara Campal
- Hospital Clínico Universitario Virgen de la Arrixaca
- Parc Taulí
- Virgen del Rocío
- Hospital de la Fe
- HCU Lozano Blesa
- Far Eastern Memorial Hospital
- Mackay Memorial Hospital - Taipei Branch
- Taipei Veterans General Hospital
- Chernihiv Medical Center of Modern Oncology of Chernihiv Regional Council
- Grigoriev Institute for Medical Radiology NAMS of Ukraine
- Communal non-profit enterprise "Khmelnytskyi Regional Antitumor Center" of Khmelnytskoyi Regional Council
- Communal non-profit enterprise "Cherkasy Regional Oncology Dispensary of Cherkasy oblast council"
- Prykarpatskyi Clinical Oncology Center of Ivano-Frankivsk Regional Council
- Peterborough City Hospital
- Royal Devon and Exeter Hospital (Wonford)
- University Hospitals Coventry and Warwickshire
- Beatson West of Scotland Cancer Centre
- St Bartholomew's Hospital-Barts Health NHS Trust
- University College London Hospital
- The Royal Marsden NHS Foundation Trust
- The Christie NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
mirvetuximab soravtansine (MIRV; IMGN853)
Investigator's choice of chemotherapy
MIRV 6 mg/kg adjusted ideal body weight (AIBW) every 3 weeks (Q3W)
Paclitaxel (Pac; 80 mg/m2) administered once per week (QW) within a 4-week cycle Pegylated liposomal doxorubicin (PLD; 40 mg/m2) administered every 4 weeks (Q4W) Topotecan (Topo; 4 mg/m2) administered either on Days 1, 8, and 15 every 4 weeks or for 5 consecutive days (1.25 mg/m2 Days 1-5) every 3 weeks (Q3W)