Clinical trial NCT02631876: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epithelial Ovarian Cancer
Primary Peritoneal Carcinoma
Fallopian Tube Cancer
Ovarian Cancer
Keywords: Epithelial ovarian cancer
Fallopian tube cancer
Primary peritoneal cancer
IMGN853
ADC
Antibody drug conjugate
ImmunoGen
Antibody
Folate receptor alpha
mirvetuximab soravtansine
Phase 3
platinum-resistant
MIRV
Lead sponsor: ImmunoGen, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Gynecologic Oncology Group
First posted: 2015-12-16
Enrollment: 366
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Participants will be randomized to either mirvetuximab soravtansine or investigator's choice chemotherapy.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Progression-Free Survival (PFS), as Assessed by BIRC Per RECIST Version 1.1 in All Participants Randomized to the Study
timeFrame: 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)
measure: PFS, as Assessed by BIRC Per RECIST Version 1.1 in Participants With High Folate Receptor Alpha Level (≥ 75% of Tumor Staining)
timeFrame: 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:
measure: Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by BIRC Per RECIST1.1
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: 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)
measure: 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
timeFrame: Baseline, Week 8/9
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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)
measure: Gynecologic Cancer Intergroup (GCIG) CA-125 Response Rate: Percentage of Participants With GCIG CA-125 Confirmed Clinical Responses
timeFrame: 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)
measure: PFS, as Assessed by Investigator Per RECIST Version 1.1
timeFrame: 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)
measure: Duration of Response (DOR), as Assessed by BIRC Per RECIST v1.1
timeFrame: From the date of first response (CR or PR) until the date of PD (maximum exposure: 86.9 weeks for mirvetuximab soravtansine arm and 62.9 weeks for IC chemotherapy arm)
measure: Area Under the Plasma Concentration-Versus Time Curve From Time of Dose Until Tlast (AUClast) of Mirvetuximab Soravtansine,Total M9346A Antibody, DM4, and S-methyl DM4
timeFrame: Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1 and 3; and Day 8 and 15 of Cycles 1 and 3
measure: Number of Participants With Anti-Drug Antibodies (ADA)
timeFrame: Pre-dose and within 5 minutes after mirvetuximab soravtansine infusion on Day 1 of Cycles 1, 2, and 4; pre-dose on Day 1 of Cycle 6
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tempe
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Women's Health Clinical Research Unit - OBGYN
state: California
city: San Diego
country: United States
facility: University of California San Diego Medical Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Norwalk
country: United States
facility: Norwalk Hospital/WCHN
state: Connecticut
city: Sarasota
country: United States
facility: Florida State University College of Medicine
state: Florida
city: Augusta
country: United States
facility: Georgia Regents University (GRU)-Medical College of Georgia (MCG) - Cancer Center
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Hinsdale
country: United States
facility: Sudarshan Sharma LTD
state: Illinois
city: Indianapolis
country: United States
facility: Community Health Network, Inc.
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Covington
country: United States
facility: Women's Cancer Care
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Shreveport
country: United States
facility: WK Physician Network Clinical Research
state: Louisiana
city: Silver Spring
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Springfield
country: United States
facility: Mercy Women's Oncology
state: Missouri
city: Reno
country: United States
facility: Center of Hope
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Camden
country: United States
facility: MD Anderson Cancer Center - Cooper Health
state: New Jersey
city: Summit
country: United States
facility: Overlook Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: The University of New Mexico Comprehensive Cancer Center - Memorial Medical Center
state: New Mexico
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center and (MSK Monmouth) and ( MSK Westchester)
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute - Carolinas Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Fairview Hospital, Moll Pavilion Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: OSU Wexner Medical Center
state: Ohio
city: Mayfield
country: United States
facility: Hillcrest Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute, LLC
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee - Womens Hospital of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Women & Infants of Rhode Island
state: Rhode Island
city: Charleston
country: United States
facility: Hollings Cancer Center
state: South Carolina
city: Austin
country: United States
facility: Texas Oncology-Austin Central
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth
state: Texas
city: The Woodlands
country: United States
facility: Texas Oncology - The Woodlands, Gynecologic Oncology
state: Texas
city: Tyler
country: United States
facility: Texas Oncology-Tyler
state: Texas
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology & Oncology
state: Washington
city: Milwaukee
country: United States
facility: Froedtert and Medical College of Wisconsin
state: Wisconsin
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Oncology Centre
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen (UZ) Leuven-Gasthuisberg
city: Libramont
country: Belgium
facility: Centre Hospitalier de l'Ardenne
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Center of Republic of Srpska
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute - Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Laval
country: Canada
facility: Hopital de la CitedelaSante
state: Quebec
city: Montreal
country: Canada
facility: Centre hospitalier de l'Université de Montréal
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre - Glen Site
state: Quebec
city: Hradec Králové
country: Czechia
facility: Porodnicka A Gynekologicka Klinika
city: Ostrava Poruba
country: Czechia
facility: University Hospital Ostrava
city: Zlín
country: Czechia
facility: Onkologicke oddeleni Krajske nemocnice T. Bati, a.s., Zlin
city: Angers
country: France
facility: Institut de Cancerologie de L'Ouest - site Paul Papin
city: Besançon
country: France
facility: CHRU Jean Minjoz
city: Bordeaux
country: France
facility: Institut Bergonie
city: Paris
country: France
facility: Cochin Hospital
city: Paris
country: France
facility: Hôpital Croix St-Simon
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon-Sud
city: Plérin
country: France
facility: Centre Armoricain de radiotherapie, Imagerie Medicale et Oncol
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Saint-Cloud
country: France
facility: Institut Curie-Hopital Rene Huguenin
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de Cancerologie de Lorraine
city: Villejuif
country: France
facility: Gustave Roussy Institution
city: Cork
country: Ireland
facility: Bon Secours Hospital
city: Dublin
country: Ireland
facility: Mater Private Hospital and Mater Misericordiae University Hospital
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: MI
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria di Bologna Policlinico S. Orsola-Malpighi
city: Brindisi
country: Italy
facility: Azienda Sanitaria Locale (ASL)
city: Faenza
country: Italy
facility: Azienda Unita Sanitaria Locale di Ravenna
city: Meldola (FC)
country: Italy
facility: Romagnolo per lo Studio e la Cura dei Tumori IRST-IRCCS - Oncologia medica
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Milan
country: Italy
facility: Fondazione IRCCS National Cancer Institute
city: Naples
country: Italy
facility: Istituto Nazionale Tumori- G. Pascale
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Moscow
country: Russian Federation
facility: LLC "VitaMed"
city: Novosibirsk
country: Russian Federation
facility: State Budget-Funded Healthcare Institution of Novosibirsk Oblast "Novosibirsk Oblast Oncology Dispensary"
city: Omsk
country: Russian Federation
facility: Budget-Funded Healthcare Institution of Omsk Oblast "Clinical Oncology Dispensary"
city: Saint Petersburg
country: Russian Federation
facility: State Budget Institution of Health "Leningrad Regional Oncologicacal Dispensary"
city: Belgrade
country: Serbia
facility: Oncology and Radiology Institute Serbia
city: Niš
country: Serbia
facility: Clinical Centre Nis, Oncology Clinic
city: Sremska Kamenica
country: Serbia
facility: Oncology Institute Vojvodina
city: Badalona
country: Spain
facility: ICO Hospital Germans Trias i Pujol
state: Barcelona
city: Donostia San Sebastian
country: Spain
facility: Onkologikoa
state: Gipuzkoa
city: A Coruña
country: Spain
facility: Hospital Teresa Herrera (CHUACoruña)
city: Barcelona
country: Spain
facility: IOR - Hospital Quiron Dexeus
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia - Unitad de Investigación Clínica
city: Córdoba
country: Spain
facility: Hospital Reina Sofia
city: Granada
country: Spain
facility: Complejo Hospitalario Granada
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: MD Anderson Cancer Center - Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Servicio de Oncología Médica Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Malaga
country: Spain
facility: Hospital Regional Universitario Malaga - Hospital Materno Infantil de Málaga
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer (HSLL)
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur, Medizinische Onkologie
state: Zurich
city: Winterthur
country: Switzerland
facility: Kantonsspital
state: Zurich
city: Geneve
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: London
country: United Kingdom
facility: UCL Cancer Institute
state: England
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - City Hospital
state: England
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Foundation Trust - Royal Preston Hospital
state: England
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH)
state: England
city: Wolverhampton
country: United Kingdom
facility: The Royal Wolverhampton Hospitals NHS Trust - New Cross Hospital - GOW
state: England
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
state: Great Britain
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Stoke-on-Trent
country: United Kingdom
facility: Cancer,Haematology and Physics Directorate, Cancer Centre Royal Stoke University
state: Staffordshire
city: Coventry
country: United Kingdom
facility: University Hospitals Coventry & Warwickshire NHS Trust, Arden Cancer Centre
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
Study officials:
affiliation: ImmunoGen, Inc.
name: CMO ImmunoGen
role: STUDY_DIRECTOR
References:
citation: 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.