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)

MIRASOL: A Randomized, Open-label, Phase 3 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

This Phase 3 study is designed to compare the efficacy and safety of mirvetuximab soravtansine vs. investigator's choice chemotherapy in patients with platinum-resistant high-grade epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of FRα. Patients will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. Folate receptor alpha (FRα) positivity will be defined by the Ventana FOLR1 (FOLR1-2.1) CDx assay.

Study Overview

• Status: Active, not recruiting
• Conditions: Fallopian Tube Cancer; Epithelial Ovarian Cancer; Peritoneal Cancer
• Intervention / Treatment: Drug: Mirvetuximab Soravtansine; Drug: Paclitaxel; Drug: Topotecan; Drug: Pegylated liposomal doxorubicin

Detailed Description

Patients will be randomized to either mirvetuximab soravtansine (MIRV) or Investigator's Choice chemotherapy (paclitaxel, PEGylated liposomal doxorubicin, or topotecan).

• Study Type: Interventional
• Enrollment (Actual): 453
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Saint Leonards, Australia, 2065
    • Royal North Shore Hospital
  • Toorak Gardens, Australia, 5065
    • Burnside War Memorial Hospital - The Brian Fricker Oncology Centre
  • New South Wales
    • New Lambton Heights, New South Wales, Australia, 2305
      • Newcastle Private Hospital
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Malvern, Victoria, Australia, 3144
      • Oncology Clinics Victoria (OCV) - Cabrini Malvern Hospital Location
• Belgium
  • Aalst, Belgium, 9300
    • OLV Ziekenhuis
  • Brasschaat, Belgium, 2390
    • AZ Klina
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen (UZA) - Borstkliniek
  • Gent, Belgium, 9000
    • AZ St-Lucas
  • Leuven, Belgium, 3000
    • UZ Leuven
• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMHAT Georgi Stranski
  • Sofia, Bulgaria, 1407
    • Acibadem City Clinic Tokuda Hospital
  • Sofia, Bulgaria, 1431
    • UMHAT "Sv. Ivan Rilski", EAD, Sofia
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Ottawa, Ontario, Canada, K1H8L6
      • The Ottawa Hospital General Campus
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Center
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre - University Health Network
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
    • Montréal, Quebec, Canada, H2X 0A9
      • Centre Hospitalier de l'Universite de Montreal
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100034
    • Peking University First Hospital
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
  • Tianjin, China, 300060
    • Tianjin Medical University Cancer Institute & Hospital
  • Anhui
    • Hefei, Anhui, China, 230000
      • Anhui Provincial Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian cancer hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University, Cancer Center
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430061
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China, 430024
      • Wuhan Union Hospital of China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
  • Jilin
    • Changchun, Jilin, China, 130031
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110801
      • Liaoning cancer hospital
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
• Czechia
  • Ostrava, Czechia, 708 52
    • Fakultni nemocnice Ostrava
  • Praha 2, Czechia, 128 51
    • Vseobecna fakultni nemocnice v Praze
  • Zlín, Czechia, 762 75
    • KNTB a.s. Zlín
• France
  • Besançon Cedex, France, 25030
    • CHRU Besançon
  • Bordeaux Cedex, France, 33076
    • Institut Bergonie
  • Lyon Cedex, France, 69373
    • Centre Léon Bérard
  • Marseille, France, 13009
    • Institut Paoli Calmettes
  • Paris, France, 75014
    • Cochin Hospital
  • Paris, France, 75960 Cedex 20
    • Groupe Hospitalier Diaconesses Croix Saint-Simon
  • Pierre-Bénite, France, 69310
    • Centre Hospitalier Lyon Sud
  • Plerin, France, 22190
    • Centre Armoricain de Radiotherapie, Imagerie medicale et Oncologie, CARIO
  • Saint Cloud, France, 92210
    • Institut Curie
  • St. Herblain CEDEX, France, 44805
    • ICO Centre Rene Gauducheau
  • Vandoeuvre les Nancy_ Cedex, France, 54519
    • Institut de Cancérologie de Lorraine
  • Villejuif Cedex, France, 94805
    • Gustave Roussy
  • Cedex
    • Angers, Cedex, France, 49055
      • Institut de cancérologie de l'ouest, site Angers
  • Cedex 9
    • Toulouse, Cedex 9, France, 31059
      • Institut Claudius Regaud
  • Cedex B.P 307
    • Lille, Cedex B.P 307, France, 59020
      • Centre Oscar Lambret
• Germany
  • Bonn, Germany, 53127
    • Universitätsklinikum Bonn
  • Dessau, Germany, 06847
    • Städtisches Klinikum Dessau, Zentrum für Klinische Studien
  • Dortmund, Germany, 44137
    • Klinikum Dortmund gGmbH / Frauenklinik
  • Freiburg, Germany, 79106
    • University Hospital Freiburg
  • Hamburg, Germany, 20357
    • Mammazentrum Hamburg am Krankenhaus Jerusalem
  • Baden-Württemberg
    • Ulm, Baden-Württemberg, Germany, 89075
      • Ulm University Hospital Klinik für Frauenheilkunde und Geburtshilfe
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37075
      • UMG Göttingen Frauenklinik
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Universitätsklinikum Carl Gustav Carus Dresden
• Israel
  • Holon, Israel, 5822012
    • Wolfson Medical Center
  • Jerusalem, Israel, POB 12000
    • Hadassah Ein Kerem Medical Center
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center
  • Ramat Gan, Israel, 5265601
    • Sheba Medical Center
  • Rehovot, Israel, 76100
    • Kaplan Medical Center
  • Safed, Israel, 13100
    • Ziv Medical Center
• Italy
  • Brescia, Italy, 25123
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
  • Lecco, Italy, 23900
    • ASST Lecco- Ospedale A.Manzoni
  • Milan, Italy, 20141
    • IRCCS - Istituto Europeo di Oncologia (The European Institute of Oncology) (IEO)
  • Naples, Italy, 80131
    • INT Pascale
  • Reggio Emilia, Italy, 42123
    • Oncologia Azienda Osc-IRCCS Reggio Emilia
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Torino, Italy, 10126
    • Azienda Ospedaliera Città della Salute e della Scienza di Torino
  • Torino, Italy, 10128
    • Ospedale Mauriziano Umberto I
  • PD
    • Padova, PD, Italy, 35128
      • IOV Istituto Oncologico
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 10408
    • National Cancer Center - Center for Uterine Cancer
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 05505
    • University of Ulsan College of Medicine - Asan Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC
  • Maastricht, Netherlands, 6229 HX
    • Maastricht UMC
  • Nijmegen, Netherlands, Postbus 9101, 6500 HB
    • Radboud University Medical Center
  • Rotterdam, Netherlands, 3015 AA
    • Erasmus Medical Center
• Poland
  • Gdańsk, Poland, 80-214
    • Medical University of Gdansk
  • Lublin, Poland, 20-081
    • Samodzielny Publiczny Szpital Kliniczny Nr 1
  • Olsztyn, Poland, 10-561
    • Wojewódzki Szpital Specjalistyczny, Oddzial Kliniczny Ginekologii Onkologiczne
  • Poznań, Poland, 61-866
    • Wielkopolskie Centrum Onkologii
  • Warszawa, Poland, 00-315
    • Szpital Kliniczny im. ks. Anny Mazowieckiej
• Portugal
  • Lisbon, Portugal, 1400-038
    • Fundação Champalimaud
  • Lisbon, Portugal, 1500-650
    • Hospital da Luz, S.A
  • Lisbon, Portugal, 1649-028
    • Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria
  • Loures, Portugal, 2674-514
    • Hospital Beatriz Angelo
• Russian Federation
  • Moscow, Russian Federation, 10
    • LLC "VitaMed"
  • St-Petersburg, Russian Federation, 194356
    • Leningrad regional oncology dispensa
  • Ufa, Russian Federation, 450054
    • State Autonomous Healthcare Institution Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
  • Omsk Oblast
    • Omsk, Omsk Oblast, Russian Federation, 644013
      • BIH of OMSK Region "Clinical Oncology Dispensary"
• Serbia
  • Belgrade, Serbia, 11000
    • Oncology and Radiology Institute Serbia
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • Sremska Kamenica, Serbia, 21204
    • Oncology Institute Vojvodina, Surgical Oncology Clinic
• Spain
  • Badalona, Spain, 8916
    • Institut Catala d'Oncologia
  • Caceres, Spain, 10003
    • H. San Pedro de Alcántara
  • Castelló, Spain, 12002
    • Hospital Provincial de Castellón
  • Madrid, Spain, 28050
    • Hospital de San Chinarro-Clara Campal
  • Murcia, Spain, 30120
    • Hospital Clinico Universitario Virgen de la Arrixaca
  • Sabadell, Spain, 8208
    • Parc Taulí
  • Sevilla, Spain, 41013
    • Virgen del Rocio
  • Valencia, Spain, 46026
    • Hospital de la Fe
  • Zaragoza, Spain, 50009
    • HCU Lozano Blesa
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Hospital Clínico de Santiago
  • Andalucia
    • Jaén, Andalucia, Spain, 23007
      • H. U. de Jaén
  • Madrid
    • San Sebastián de los Reyes, Madrid, Spain, 28702
      • Hospital Universitario Infanta Sofía
• Taiwan
  • New Taipei City, Taiwan, 220
    • Far Eastern Memorial Hospital
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei City, Taiwan, 10449
    • Mackay Memorial Hospital - Taipei Branch
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Communal non-profit enterprise "Cherkasy Regional Oncology Dispensary of Cherkasy oblast council"
  • Ivano-Frankivsk, Ukraine, 76018
    • Prykarpatskyi Clinical Oncology Center of Ivano-Frankivsk Regional Council
  • Chernihiv Region
    • Chernihiv, Chernihiv Region, Ukraine, 14029
      • Chernihiv Medical Center of Modern Oncology of Chernihiv Regional Council
  • Kharkiv Region
    • Kharkiv, Kharkiv Region, Ukraine, 61024
      • Grigoriev Institute for Medical Radiology NAMS of Ukraine
  • Khmelnytskyi Region
    • Khmelnytskyi, Khmelnytskyi Region, Ukraine, 29009
      • Communal non-profit enterprise "Khmelnytskyi Regional Antitumor Center" of Khmelnytskoyi Regional Council
• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • University Hospitals Coventry and Warwickshire
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust
  • London, United Kingdom, NW1 2PG
    • University College London Hospital
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital-Barts Health NHS Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Cambridgeshire
    • Peterborough, Cambridgeshire, United Kingdom, PE3 9GZ
      • Peterborough City Hospital
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital (Wonford)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham (UAB) GYN Oncology
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Women's Cancer Care
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
    • Phoenix, Arizona, United States, 85016
      • Arizona Oncology Associates, PC - HAL - USOR
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center
    • Tucson, Arizona, United States, 85711
      • USOR: Arizona Oncology Associates, PC - HOPE
  • California
    • Los Angeles, California, United States, 90095
      • UCLA - JCCC Dept of OBGYN - Women's Health Clinical Research Unit
    • Newport Beach, California, United States, 92663
      • Hoag Cancer Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Sylmar, California, United States, 91324
      • Olive View - UCLA Medical Center
    • Vallejo, California, United States, 94589
      • Kaiser Permanente Oncology Clinical Trials
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • USOR: Rocky Mountain Cancer Centers
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialist South Division
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
    • Saint Petersburg, Florida, United States, 33701
      • Women's Care Florida / Women's Cancer Associates
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialist North Division
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
    • Tallahassee, Florida, United States, 32308
      • Florida Cancer Specialists
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialist East Division
  • Georgia
    • Savannah, Georgia, United States, 31404
      • Memorial University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Pacific Health - Kapiolani Medical Center for Women and Children
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Illinois Cancer Specialists
    • Chicago, Illinois, United States, 60637
      • University Of Chicago
    • Hinsdale, Illinois, United States, 60521
      • Dr. Sudarshan K. Sharma, Ltd.
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Community Health Network
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • St. Elizabeth Healthcare
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochnser Medical Center Jefferson
    • Shreveport, Louisiana, United States, 771103
      • WK Physicians Network/Gynecologic Oncology Associates
  • Maryland
    • Silver Spring, Maryland, United States, 20902
      • Holy Cross Hospital
    • Silver Spring, Maryland, United States, 20902
      • USOR: Maryland Oncology Hematology, P.A.
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
    • Worcester, Massachusetts, United States, 01605
      • University of Massachusetts
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
    • Woodbury, Minnesota, United States, 55125
      • USOR: Minnesota Oncology Hematology, PA
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • HCA Midwest Kansas City/ Sarah Cannon
  • Montana
    • Great Falls, Montana, United States, 59405
      • Sletten Cancer Institute
  • Nevada
    • Reno, Nevada, United States, 89511
      • Center of Hope
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450
      • The Valley Hospital, Inc
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas Outpatient Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • USOR: OHC - Oncology_Hematology Care Clinical Trials, Inc.
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43215
      • Columbus NCORP
    • Columbus, Ohio, United States, 43219
      • Zangmeister Cancer Center
    • Hilliard, Ohio, United States, 43026
      • The Ohio State University Wexner Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute
  • Oregon
    • Eugene, Oregon, United States, 97401
      • USOR: Willamette Valley Cancer Institute and Research Center
    • Portland, Oregon, United States, 97210
      • Legacy Gynecologic Oncology
    • Portland, Oregon, United States, 97227
      • USOR: Northwest Cancer Specialists, P.C.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • West Penn Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Women's Hospital-UPMC
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women & Infants Hospital of Rhode Island
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology / Sarah Cannon Research Institute
  • Texas
    • Austin, Texas, United States, 78745
      • USOR: Texas Oncology-South Austin
    • Fort Worth, Texas, United States, 76104
      • USOR: Texas Oncology - Fort Worth Cancer Center
    • Houston, Texas, United States, 77030
      • University of Texas, Memorial Hermann
    • McAllen, Texas, United States, 78503
      • USOR: Texas Oncology - McAllen South Second
    • San Antonio, Texas, United States, 78240
      • USOR: Texas Oncology - San Antonio
    • Sugar Land, Texas, United States, 77479
      • USOR: Texas Oncology, P.A.
    • The Woodlands, Texas, United States, 77380
      • USOR: Texas Oncology - The Woodlands, Gynecologic Oncology
    • Tyler, Texas, United States, 75702
      • USOR: Texas Oncology - Tyler
    • Webster, Texas, United States, 77598
      • USOR: Texas Oncology, P.A.
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University Of Virginia Health System
    • Gainesville, Virginia, United States, 20155
      • USOR: Virginia Cancer Specialists, PC
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology & Oncology
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University- MBRCC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female patients ≥ 18 years of age
2. Patients must have a confirmed diagnosis of high-grade serious epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer

3. Patients must have platinum-resistant disease:

   1. 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
   2. 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
4. Patients must have progressed radiographically on or after their most recent line of therapy
5. 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
6. Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1 (FOLR-2.1) CDx assay
7. Patients must have at least one lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)

8. 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:

   1. Adjuvant ± neoadjuvant considered one line of therapy
   2. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as part of the preceding line of therapy (ie, not counted independently)
   3. Therapy changed due to toxicity in the absence of progression will be considered as part of the same line (ie, not counted independently)
   4. Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
9. Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1

10. Time from prior therapy:

    1. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter)
    2. Focal radiation completed at least 2 weeks prior to first dose of study drug
11. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities
12. 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

13. Patients must have adequate hematologic, liver and kidney functions defined as:

    1. 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
    2. Platelet count ≥ 100 x 10^9/L (100,000/μL) without platelet transfusion in the prior 10 days
    3. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days
    4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
    6. Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN
    7. Serum albumin ≥ 2 g/dL
14. 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
15. 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
16. WCBP must have a negative pregnancy test within 4 days prior to the first dose of study drug

Exclusion Criteria:

1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade or borderline ovarian tumor
2. 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
3. Patients with prior wide-field radiotherapy (RT) affecting at least 20% of the bone marrow
4. Patients with > Grade 1 peripheral neuropathy per CTCAE v5.0
5. 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

6. Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:

   1. Active hepatitis B or C infection (whether or not on active antiviral therapy)
   2. HIV infection
   3. Active cytomegalovirus infection
   4. 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
7. Patients with history of multiple sclerosis or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)

8. Patients with clinically significant cardiac disease including, but not limited to, any one of the following:

   1. Myocardial infarction ≤ 6 months prior to first dose
   2. Unstable angina pectoris
   3. Uncontrolled congestive heart failure (New York Heart Association > class II)
   4. Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
   5. Uncontrolled cardiac arrhythmias
9. 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
10. Patients with a history of hemorrhagic or ischemic stroke within six months prior to randomization
11. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
12. Patients with a previous clinical diagnosis of non-infectious interstitial lung disease (ILD), including noninfectious pneumonitis
13. Patients with required use of folate-containing supplements (eg, folate deficiency)
14. Patients with prior hypersensitivity to monoclonal antibodies
15. Women who are pregnant or lactating
16. Patients with prior treatment with MIRV or other FRα-targeting agents
17. Patients with untreated or symptomatic central nervous system (CNS) metastases
18. 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
19. Prior known hypersensitivity reactions to study drugs and/or any of their excipients
20. 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
21. Simultaneous participation in another research study, in countries or localities where this is the health authority guidance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mirvetuximab soravtansine (MIRV; IMGN853); MIRV 6 mg/kg adjusted ideal body weight (AIBW) every 3 weeks (Q3W)	Drug: Mirvetuximab Soravtansine; Mirvetuximab soravtansine is an antibody drug conjugate designed to target folate receptor α (FRα). It consists of the humanized anti-FRα mAb M9346A attached via a cleavable disulfide linker to the cytotoxic maytansinoid, DM4.; Other Names: IMGN853; MIRV
Active Comparator: Investigator's choice of chemotherapy; 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)	Drug: Paclitaxel; Paclitaxel is a taxane that can stabilize microtubules to inhibit cell division. It was approved for treatment of recurrent epithelial ovarian cancer.; Drug: Topotecan; Topotecan induces irreversible DNA damage. It inhibits topoisomerase 1, leading to both single and double strand DNA break that eventually promote apoptosis. Topotecan was approved for treatment of epithelial ovarian cancer after failure of initial or subsequent chemotherapy.; Drug: Pegylated liposomal doxorubicin; Pegylated liposomal doxorubicin is a standard chemotherapy regimen used for treating platinum-resistant ovarian cancer. The active component doxorubicin is an anthracycline that intercalates DNA, leading to inhibition of replication and subsequently, the inhibition of proper cell division.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	The time from date of randomization until Investigator-assessed progressive disease or death, whichever occurs first.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Adverse events (AEs) will be evaluated according to the NCI CTCAE v5.0. AEs will be coded using the latest Medical Dictionary for Regulatory Activities (MedDRA) version and summarized per system organ class (SOC) and preferred term (PT).	Up to 2 years
Objective Response Rate (ORR)	Objective response includes best response of complete response (CR) or partial response (PR).	Up to 2 years
Overall survival	The time from date of randomization until the date of death	Up to 2 years
Primary patient-reported outcomes	The number of patients achieving at least 15 point absolute improvement at Week 8 or Week 9 in the abdominal/GI scale of the European Organization for Research and Treatment of Cancer (EORTC) ovarian cancer specific quality of life questionnaire (QLQ-OV28). A higher score represents a better quality of life.	Up to 2 years
Duration of response (DOR)	The time from initial response until Investigator-assessed progressive disease for all patients who achieve a confirmed objective response	Up to 2 years
CA-125 response	Serum CA-125 response determined using the GCIG criteria	Up to 2 years
Progression-free survival 2 (PFS 2)	The time from date of randomization until second disease progression or death whichever occurs first. Results will be summarized by arm	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient-reported outcomes using EORTC QLQ-C30 questionnaires	The EORTC QLQ-C30 questionnaires will be used to collect data on the patient's functioning, health-related QOL, disease symptoms and health status. A higher score represents a higher response level.	Up to 2 years
Patient-reported outcomes using EQ-5D-5L questionnaires	The EuroQol-5 Dimension 5-level (EQ-5D-5L) questionnaires will be used to collect data on the patient's functioning, health-related QOL, disease symptoms and health status. A higher score represents a higher response level.	Up to 2 years
Pharmacokinetic parameters	Plasma samples will be collected to determine the concentration of MIRV (antibody-drug conjugate, total antibody, free DM4, S-methyl DM4 and possibly other metabolites). Summary statistics of the concentration at each time point (nominal time) will be presented. Graphical presentation of the data may also be completed using nominal time.	Up to 2 years
Immunogenicity	The presence of anti-drug antibodies to mirvetuximab soravtansine	Up to 2 years
Identification of soluble FRα levels and other biomarkers		Up to 2 years
Patient-reported outcomes using PGIS questionnaires	The Patient Global Impression of Severity (PGIS) questionnaires will be used to collect data on the patient's perception of overall cancer symptom severity. This is a single question survey.	Up to 2 years

Collaborators and Investigators

• Sponsor: ImmunoGen, Inc.
• Collaborators: Gynecologic Oncology Group; European Network of Gynaecological Oncological Trial Groups (ENGOT)
• Investigators: Study Director: Michael Method, MPH, MBA, ImmunoGen, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2019
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): April 1, 2024

Study Registration Dates

• First Submitted: December 17, 2019
• First Submitted That Met QC Criteria: December 20, 2019
• First Posted (Actual): December 24, 2019

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Epithelial Ovarian Cancer; Platinum-resistant; Phase 3; Peritoneal Cancer; Fallopian Tube Cancer; IMGN853; Folate-receptor alpha expression; Antibody-drug conjugate; mirvetuximab soravtansine
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Topoisomerase I Inhibitors; Paclitaxel; Doxorubicin; Liposomal doxorubicin; Topotecan; Maytansine
• Other Study ID Numbers: IMGN853-0416; 2019-003509-80 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No