A Study of Mirvetuximab Soravtansine vs. Investigator's Choice of Chemotherapy in Women With Folate Receptor (FR) Alpha Positive Advanced Epithelial Ovarian Cancer (EOC), Primary Peritoneal or Fallopian Tube Cancer
FORWARD I
FORWARD I: A Randomized, Open Label Phase 3 Study to Evaluate the Safety and Efficacy of Mirvetuximab Soravtansine (IMGN853) Versus Investigator's Choice of Chemotherapy in Women With Folate Receptor Alpha Positive Advanced Epithelial Ovarian Cancer, Primary Peritoneal Cancer or Fallopian Tube Cancer
1 other identifier
interventional
366
13 countries
131
Brief Summary
This is a Phase 3, open label, randomized study designed to compare the safety and efficacy of mirvetuximab soravtansine to that of selected single-agent chemotherapy (Investigator's choice) in women with platinum-resistant FR-alpha positive advanced EOC, primary peritoneal cancer and/or fallopian tube cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2016
Typical duration for phase_3
131 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 10, 2015
CompletedFirst Posted
Study publicly available on registry
December 16, 2015
CompletedStudy Start
First participant enrolled
March 2, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2020
CompletedResults Posted
Study results publicly available
June 9, 2020
CompletedOctober 14, 2020
September 1, 2020
2.8 years
December 10, 2015
May 6, 2020
September 24, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Progression-Free Survival (PFS), as Assessed by BIRC Per RECIST Version 1.1 in All Participants Randomized to the Study
PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the sum of the longest diameters (SoD) of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
PFS, as Assessed by BIRC Per RECIST Version 1.1 in Participants With High Folate Receptor Alpha Level (≥ 75% of Tumor Staining)
PFS was defined as the time from randomization until PD or death whichever occurred first, estimated using the Kaplan-Meier method. PD: At least a 20% increase in the SoD of target lesion, taken as reference the smallest (nadir) SoD since and including baseline. In addition to the relative increase of 20%, the SoD must also demonstrate an absolute increase of at least 5 mm. Unequivocal progression of non-target lesions and appearance of new lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
From the date of randomization until the time of death or PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Secondary Outcomes (9)
Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by BIRC Per RECIST1.1
From randomization until first BOR of CR or PR (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Overall Survival (OS)
From the date of randomization until the time of death (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Number of Participants Achieving at Least a 15% (≥ 15-Point) Absolute Improvement From Baseline on the EORTC QLQ-OV28 Abdominal/Gastrointestinal (AB/GI) Symptom Subscale at Week 8/9 Assessment
Baseline, Week 8/9
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
From first dose of study drug up to 30 days after last dose of study drug (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
Gynecologic Cancer Intergroup (GCIG) CA-125 Response Rate: Percentage of Participants With GCIG CA-125 Confirmed Clinical Responses
From first dose of study drug until CA-125 response (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
- +4 more secondary outcomes
Study Arms (2)
Mirvetuximab Soravtansine
EXPERIMENTALParticipants will receive mirvetuximab soravtansine at 6 milligrams/kilogram (mg/kg) adjusted ideal body weight (AIBW) administered intravenously (IV) on Day 1 of a 3 week cycle. Participants will continue to receive study drug until they experience progressive disease (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (as assessed by the blinded independent review committee \[BIRC\]), experience unacceptable toxicity, or withdraw consent, whichever comes first, or until the sponsor terminate the study. (Maximum exposure: 86.9 weeks)
Investigator's Choice (IC) Chemotherapy
EXPERIMENTALParticipants will receive a dose of IC chemotherapeutic agent calculated using body surface area (BSA). Paclitaxel will be administered at 80 milligrams/square meter (mg/m\^2) as a 1-hour IV infusion on Days 1, 8, 15, and 22 of a 4-week cycle; or topotecan will be administered at 4 mg/m\^2 over 30 minutes on Days 1, 8, and 15 of a 4-week cycle. Alternatively, topotecan could be administered at 1.25 mg/m\^2 over 30 minutes on Days 1 to 5 of a 3-week cycle; or pegylated liposomal doxorubicin will be administered at 40 mg/m\^2 as a 1 mg/minute IV infusion on Day 1 of a 4-week cycle. After Cycle 1, if tolerated, pegylated liposomal doxorubicin could be administered as a 1-hour infusion. Participants will continue to receive study drug until they experience PD per RECIST version 1.1 (as assessed by BIRC), experience unacceptable toxicity, or withdraw consent, whichever comes first, or until the sponsor terminate the study. (Maximum exposure: 62.9 weeks)
Interventions
Mirvetuximab Soravtansine will be administered per dose and schedule specified in the arm.
Paclitaxel will be administered per dose and schedule specified in the arm.
Pegylated liposomal doxorubicin will be administered per dose and schedule specified in the arm.
Topotecan will be administered per dose and schedule specified in the arm.
Eligibility Criteria
You may qualify if:
- Participants must be diagnosed with advanced epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer
- Participants must have folate receptor alpha positive tumor expression as defined in the protocol
- Participants must have platinum-resistant ovarian cancer, defined as progression within 6 months from completion of a minimum of four cycles of platinum-containing therapy.
- Participants must have received at least one but no more than three prior systemic treatment regimens and for whom single-agent chemotherapy is appropriate as the next line of treatment
- Participants must have at least one lesion that meets the definition of measurable disease by RECIST 1.1
You may not qualify if:
- Diagnosis of clear cell, low grade ovarian cancer or mixed tumors
- Participants with primary platinum-refractory disease
- Serious concurrent illness or clinically relevant active infection as defined in the protocol
- Prior treatment with mirvetuximab soravtansine
- Women who are pregnant or breast feeding
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- ImmunoGen, Inc.lead
- Gynecologic Oncology Groupcollaborator
Study Sites (131)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Arizona Oncology Associates, PC - HAL
Tempe, Arizona, 85284, United States
Arizona Oncology Associates, PC - HOPE
Tucson, Arizona, 85711, United States
UCLA Women's Health Clinical Research Unit - OBGYN
Los Angeles, California, 90095, United States
University of California San Diego Medical Center
San Diego, California, 92093, United States
California Pacific Medical Center
San Francisco, California, 94118, United States
Kaiser Permanente Medical Center
Vallejo, California, 94589, United States
Yale University School of Medicine
New Haven, Connecticut, 06520, United States
Norwalk Hospital/WCHN
Norwalk, Connecticut, 06856, United States
Florida State University College of Medicine
Sarasota, Florida, 34239, United States
Georgia Regents University (GRU)-Medical College of Georgia (MCG) - Cancer Center
Augusta, Georgia, 30912, United States
Rush University Medical Center
Chicago, Illinois, 60629, United States
Sudarshan Sharma LTD
Hinsdale, Illinois, 60521, United States
Community Health Network, Inc.
Indianapolis, Indiana, 46184, United States
Indiana University School of Medicine
Indianapolis, Indiana, 46202, United States
Norton Cancer Institute
Louisville, Kentucky, 40241, United States
Women's Cancer Care
Covington, Louisiana, 70433, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121, United States
WK Physician Network Clinical Research
Shreveport, Louisiana, 71101, United States
Holy Cross Hospital
Silver Spring, Maryland, 20902, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01605, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
Mercy Women's Oncology
Springfield, Missouri, 65804, United States
Center of Hope
Reno, Nevada, 89502, United States
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
MD Anderson Cancer Center - Cooper Health
Camden, New Jersey, 08103, United States
Overlook Medical Center
Summit, New Jersey, 07901, United States
The University of New Mexico Comprehensive Cancer Center - Memorial Medical Center
Albuquerque, New Mexico, 87131, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
Icahn School of Medicine at Mount Sinai
New York, New York, 10029, United States
Memorial Sloan Kettering Cancer Center and (MSK Monmouth) and ( MSK Westchester)
New York, New York, 10065, United States
Levine Cancer Institute - Carolinas Medical Center
Charlotte, North Carolina, 28204, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267, United States
Fairview Hospital, Moll Pavilion Cancer Center
Cleveland, Ohio, 44111, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
OSU Wexner Medical Center
Columbus, Ohio, 43210, United States
Hillcrest Hospital
Mayfield, Ohio, 44124, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oklahoma Cancer Specialists and Research Institute, LLC
Tulsa, Oklahoma, 74146, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
Magee - Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213, United States
Women & Infants of Rhode Island
Providence, Rhode Island, 02905, United States
Hollings Cancer Center
Charleston, South Carolina, 29425, United States
Texas Oncology-Austin Central
Austin, Texas, 78731, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Texas Oncology - Fort Worth
Fort Worth, Texas, 76104, United States
Texas Oncology - The Woodlands, Gynecologic Oncology
The Woodlands, Texas, 77380, United States
Texas Oncology-Tyler
Tyler, Texas, 75702, United States
Kadlec Clinic Hematology & Oncology
Kennewick, Washington, 99336, United States
Froedtert and Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
AZ Groeninge - Oncology Centre
Kortrijk, 8500, Belgium
Universitaire Ziekenhuizen (UZ) Leuven-Gasthuisberg
Leuven, B-3000, Belgium
Centre Hospitalier de l'Ardenne
Libramont, 6800, Belgium
University Clinical Center of Republic of Srpska
Banja Luka, 78 000, Bosnia and Herzegovina
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2, Canada
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2, Canada
Juravinski Cancer Centre
Hamilton, Ontario, L8V 5C2, Canada
London Health Sciences Centre
London, Ontario, N6A 4L6, Canada
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H8L6, Canada
Sunnybrook Research Institute - Odette Cancer Centre
Toronto, Ontario, M4N 3M5, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9, Canada
Hopital de la CitedelaSante
Laval, Quebec, H7M 3L9, Canada
Centre hospitalier de l'Université de Montréal
Montreal, Quebec, H2X 0A9, Canada
McGill University Health Centre - Glen Site
Montreal, Quebec, H4A 3J1, Canada
Porodnicka A Gynekologicka Klinika
Hradec Králové, 500 05, Czechia
University Hospital Ostrava
Ostrava Poruba, 708 52, Czechia
Onkologicke oddeleni Krajske nemocnice T. Bati, a.s., Zlin
Zlín, 76275, Czechia
Institut de Cancerologie de L'Ouest - site Paul Papin
Angers, 49055, France
CHRU Jean Minjoz
Besançon, 25030, France
Institut Bergonie
Bordeaux, 33076, France
Cochin Hospital
Paris, 75014, France
Hôpital Croix St-Simon
Paris, 75020, France
Centre Hospitalier Lyon-Sud
Pierre-Bénite, 69495, France
Centre Armoricain de radiotherapie, Imagerie Medicale et Oncol
Plérin, 22190, France
Centre Eugene Marquis
Rennes, 35042, France
Institut Curie-Hopital Rene Huguenin
Saint-Cloud, 92210, France
Institut Claudius Regaud
Toulouse, 31059, France
Institut de Cancerologie de Lorraine
Vandœuvre-lès-Nancy, 54519, France
Gustave Roussy Institution
Villejuif, 94800, France
Bon Secours Hospital
Cork, Ireland
Mater Private Hospital and Mater Misericordiae University Hospital
Dublin, Ireland
Istituto Europeo di Oncologia
Milan, MI, 20141, Italy
Azienda Ospedaliero Universitaria di Bologna Policlinico S. Orsola-Malpighi
Bologna, 40138, Italy
Azienda Sanitaria Locale (ASL)
Brindisi, 72100, Italy
Azienda Unita Sanitaria Locale di Ravenna
Faenza, 48018, Italy
Romagnolo per lo Studio e la Cura dei Tumori IRST-IRCCS - Oncologia medica
Meldola (FC), 47014, Italy
Ospedale San Raffaele
Milan, 20132, Italy
Fondazione IRCCS National Cancer Institute
Milan, 20133, Italy
Istituto Nazionale Tumori- G. Pascale
Naples, 80131, Italy
Policlinico Universitario Agostino Gemelli
Roma, 00168, Italy
LLC "VitaMed"
Moscow, 121309, Russia
State Budget-Funded Healthcare Institution of Novosibirsk Oblast "Novosibirsk Oblast Oncology Dispensary"
Novosibirsk, 630108, Russia
Budget-Funded Healthcare Institution of Omsk Oblast "Clinical Oncology Dispensary"
Omsk, 644013, Russia
State Budget Institution of Health "Leningrad Regional Oncologicacal Dispensary"
Saint Petersburg, 191014, Russia
Oncology and Radiology Institute Serbia
Belgrade, 11 000, Serbia
Oncology Institute Vojvodina
Kamenitz, 21 204, Serbia
Clinical Centre Nis, Oncology Clinic
Niš, 18 000, Serbia
ICO Hospital Germans Trias i Pujol
Badalona, Barcelona, 08916, Spain
Onkologikoa
Donostia / San Sebastian, Gipuzkoa, 20014, Spain
Hospital Teresa Herrera (CHUACoruña)
A Coruña, 15006, Spain
IOR - Hospital Quiron Dexeus
Barcelona, 08028, Spain
Hospital Vall D'Hebron
Barcelona, 08035, Spain
Institut Català d'Oncologia - Unitad de Investigación Clínica
Barcelona, 08908, Spain
Hospital Reina Sofia
Córdoba, 14004, Spain
Complejo Hospitalario Granada
Granada, 18014, Spain
Hospital Universitario Gregorio Maranon
Madrid, 28007, Spain
MD Anderson Cancer Center - Madrid
Madrid, 28033, Spain
Hospital Universitario Ramon Y Cajal
Madrid, 28034, Spain
Servicio de Oncología Médica Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Universitario HM Sanchinarro
Madrid, 28050, Spain
Hospital Regional Universitario Malaga - Hospital Materno Infantil de Málaga
Málaga, 29011, Spain
Hospital Son Llatzer (HSLL)
Palma de Mallorca, 07198, Spain
Instituto Valenciano de Oncologia
Valencia, 46009, Spain
Kantonsspital Winterthur, Medizinische Onkologie
Winterthur, Canton of Zurich, 8401, Switzerland
Kantonsspital
Winterthur, Canton of Zurich, 8401, Switzerland
Hopitaux Universitaires de Geneve
Geneva, 1205, Switzerland
UCL Cancer Institute
London, England, WC1E 6BT, United Kingdom
The Christie NHS Foundation Trust
Manchester, England, M20 4BX, United Kingdom
Nottingham University Hospitals NHS Trust - City Hospital
Nottingham, England, NG5 1PB, United Kingdom
Lancashire Teaching Hospitals NHS Foundation Trust - Royal Preston Hospital
Preston, England, PR2 9HT, United Kingdom
The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH)
Sutton, England, SM2 5PT, United Kingdom
The Royal Wolverhampton Hospitals NHS Trust - New Cross Hospital - GOW
Wolverhampton, England, WV10 OQP, United Kingdom
Peterborough City Hospital
Peterborough, Great Britain, PE3 9GZ, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, G12 0YN, United Kingdom
Cancer,Haematology and Physics Directorate, Cancer Centre Royal Stoke University
Stoke-on-Trent, Staffordshire, ST4 6QG, United Kingdom
University Hospitals Coventry & Warwickshire NHS Trust, Arden Cancer Centre
Coventry, CV2 2DX, United Kingdom
Mount Vernon Cancer Centre
Northwood, HA6 2RN, United Kingdom
Related Publications (1)
Moore KN, Oza AM, Colombo N, Oaknin A, Scambia G, Lorusso D, Konecny GE, Banerjee S, Murphy CG, Tanyi JL, Hirte H, Konner JA, Lim PC, Prasad-Hayes M, Monk BJ, Pautier P, Wang J, Berkenblit A, Vergote I, Birrer MJ. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I. Ann Oncol. 2021 Jun;32(6):757-765. doi: 10.1016/j.annonc.2021.02.017. Epub 2021 Mar 2.
PMID: 33667670DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- CMO, ImmunoGen
- Organization
- ImmunoGen, Inc
Study Officials
- STUDY DIRECTOR
CMO ImmunoGen
ImmunoGen, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 10, 2015
First Posted
December 16, 2015
Study Start
March 2, 2016
Primary Completion
January 1, 2019
Study Completion
January 1, 2020
Last Updated
October 14, 2020
Results First Posted
June 9, 2020
Record last verified: 2020-09