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
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.
Key Facts
Lead Sponsor
ImmunoGen, Inc.
Enrollment
366
Start Date
2016-03-02
Completion Date
2019-01-01
Study Type
INTERVENTIONAL
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
Interventions
Conditions
Eligibility
Age Range
18 Years+
Sex
FEMALE
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
Outcome Measures
Primary Outcomes
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.
Time frame: 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.
Time frame: 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
Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by BIRC Per RECIST1.1
ORR was defined as percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). CR: Disappearance of all target or non-target lesions. All pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR: At least 30 percent (%) decrease in the SoD of target lesions, taking as reference the baseline SoD.
Time frame: 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)
OS was defined as the time from the date of randomization until the date of death from any cause. Participants who did not experience the event of death were censored at their last date known to be alive. OS was estimated using the Kaplan-Meier method.
Time frame: 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
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer 28 (EORTC QLQ-OV28) is a 28-item ovarian cancer supplemental module. It comprises of 6 symptom scales (AB/GI symptoms, peripheral neuropathy, other chemotherapy side-effects, hormonal symptoms, body image, attitude to disease, treatment), and sexual functioning. Participants were asked to indicate extent to which they experienced AB/GI symptoms. Participants responded on a scale of 1-4(1=not at all, 2=a little, 3=quite a bit, 4=very much) to following: Did you have abdominal pain? Did you have a bloated feeling in your abdomen? Did you have problems with your clothes feeling too tight? Did you experience any change in bowel habit as a result of your disease or treatment? Were you troubled by passing wind/gas/flatulence? Have you felt full too quickly after beginning to eat? Have you had indigestion/heartburn? Data were transformed to a scale from 0-100. Lower scores=better health.
Time frame: Baseline, Week 8/9
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Adverse event (AE): any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to study drug. Severity: graded per National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) v4.03 on following scale: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death. Relation of AE to treatment was determined by investigator. Serious AEs: death, life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent/significant disability or incapacity, congenital anomaly or birth defect, or an important medical event that required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs: any AE that emerged on or after the first dose, and within 30 days of the last dose. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported AEs module.
Time frame: 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
CA-125 Response rate wasdefined as the number of participants with a CA-125 confirmed response divided by the number of participants in the CA-125 response-evaluable population multiplied by 100.
Time frame: 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)
PFS, as Assessed by Investigator Per RECIST Version 1.1
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.
Time frame: 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)
Duration of Response (DOR), as Assessed by BIRC Per RECIST v1.1
DOR was defined as the time from the date of the first response (CR or PR), whichever was recorded first, until the date of PD. 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. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. DOR was only defined for participants who had a BOR of CR or PR using the method of Kaplan-Meier.
Time frame: 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)
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
PK parameters were calculated using standard non-compartmental methods.
Time frame: 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
Number of Participants With Anti-Drug Antibodies (ADA)
An electrochemiluminescent method was used for the detection of anti-mirvetuximab soravtansine antibodies in plasma from samples collected in dipotassium ethylenediaminetetraacetic acid (K2EDTA) tubes. The qualitative assay was designed to detect anti-mirvetuximab soravtansine antibodies in human plasma.
Time frame: 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
Locations
University of Alabama at Birmingham, Birmingham, United States
Arizona Oncology Associates, PC - HAL, Tempe, United States
Arizona Oncology Associates, PC - HOPE, Tucson, United States
UCLA Women's Health Clinical Research Unit - OBGYN, Los Angeles, United States
University of California San Diego Medical Center, San Diego, United States
California Pacific Medical Center, San Francisco, United States
Kaiser Permanente Medical Center, Vallejo, United States
Yale University School of Medicine, New Haven, United States
Norwalk Hospital/WCHN, Norwalk, United States
Florida State University College of Medicine, Sarasota, United States
Georgia Regents University (GRU)-Medical College of Georgia (MCG) - Cancer Center, Augusta, United States
Rush University Medical Center, Chicago, United States
Sudarshan Sharma LTD, Hinsdale, United States
Community Health Network, Inc., Indianapolis, United States
Indiana University School of Medicine, Indianapolis, United States
Norton Cancer Institute, Louisville, United States
Women's Cancer Care, Covington, United States
Ochsner Clinic Foundation, New Orleans, United States
WK Physician Network Clinical Research, Shreveport, United States
Holy Cross Hospital, Silver Spring, United States
Massachusetts General Hospital, Boston, United States
Dana-Farber Cancer Institute, Boston, United States
University of Massachusetts Memorial Medical Center, Worcester, United States
Karmanos Cancer Institute, Detroit, United States
Henry Ford Hospital, Detroit, United States
Mercy Women's Oncology, Springfield, United States
Center of Hope, Reno, United States
Dartmouth-Hitchcock Medical Center, Lebanon, United States
MD Anderson Cancer Center - Cooper Health, Camden, United States
Overlook Medical Center, Summit, United States
The University of New Mexico Comprehensive Cancer Center - Memorial Medical Center, Albuquerque, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone, New York, United States
Icahn School of Medicine at Mount Sinai, New York, United States
Memorial Sloan Kettering Cancer Center and (MSK Monmouth) and ( MSK Westchester), New York, United States
Levine Cancer Institute - Carolinas Medical Center, Charlotte, United States
University of Cincinnati Medical Center, Cincinnati, United States
Fairview Hospital, Moll Pavilion Cancer Center, Cleveland, United States
Cleveland Clinic, Cleveland, United States
OSU Wexner Medical Center, Columbus, United States
Hillcrest Hospital, Mayfield, United States
University of Oklahoma Health Sciences Center, Oklahoma City, United States
Oklahoma Cancer Specialists and Research Institute, LLC, Tulsa, United States
University of Pennsylvania, Philadelphia, United States
Magee - Womens Hospital of UPMC, Pittsburgh, United States
Women & Infants of Rhode Island, Providence, United States
Hollings Cancer Center, Charleston, United States
Texas Oncology-Austin Central, Austin, United States
University of Texas Southwestern Medical Center, Dallas, United States
Texas Oncology - Fort Worth, Fort Worth, United States
Texas Oncology - The Woodlands, Gynecologic Oncology, The Woodlands, United States
Texas Oncology-Tyler, Tyler, United States
Kadlec Clinic Hematology & Oncology, Kennewick, United States
Froedtert and Medical College of Wisconsin, Milwaukee, United States
Cliniques Universitaires Saint-Luc, Brussels, Belgium
AZ Groeninge - Oncology Centre, Kortrijk, Belgium
Universitaire Ziekenhuizen (UZ) Leuven-Gasthuisberg, Leuven, Belgium
Centre Hospitalier de l'Ardenne, Libramont, Belgium
University Clinical Center of Republic of Srpska, Banja Luka, Bosnia and Herzegovina
Tom Baker Cancer Centre, Calgary, Canada
Cross Cancer Institute, Edmonton, Canada
Juravinski Cancer Centre, Hamilton, Canada
London Health Sciences Centre, London, Canada
The Ottawa Hospital Cancer Centre, Ottawa, Canada
Sunnybrook Research Institute - Odette Cancer Centre, Toronto, Canada
Princess Margaret Cancer Centre, Toronto, Canada
Hopital de la CitedelaSante, Laval, Canada
Centre hospitalier de l'Université de Montréal, Montreal, Canada
McGill University Health Centre - Glen Site, Montreal, Canada
Porodnicka A Gynekologicka Klinika, Hradec Králové, Czechia
University Hospital Ostrava, Ostrava Poruba, Czechia
Onkologicke oddeleni Krajske nemocnice T. Bati, a.s., Zlin, Zlín, Czechia
Institut de Cancerologie de L'Ouest - site Paul Papin, Angers, France
CHRU Jean Minjoz, Besançon, France
Institut Bergonie, Bordeaux, France
Cochin Hospital, Paris, France
Hôpital Croix St-Simon, Paris, France
Centre Hospitalier Lyon-Sud, Pierre-Bénite, France
Centre Armoricain de radiotherapie, Imagerie Medicale et Oncol, Plérin, France
Centre Eugene Marquis, Rennes, France
Institut Curie-Hopital Rene Huguenin, Saint-Cloud, France
Institut Claudius Regaud, Toulouse, France
Institut de Cancerologie de Lorraine, Vandœuvre-lès-Nancy, France
Gustave Roussy Institution, Villejuif, France
Bon Secours Hospital, Cork, Ireland
Mater Private Hospital and Mater Misericordiae University Hospital, Dublin, Ireland
Istituto Europeo di Oncologia, Milan, Italy
Azienda Ospedaliero Universitaria di Bologna Policlinico S. Orsola-Malpighi, Bologna, Italy
Azienda Sanitaria Locale (ASL), Brindisi, Italy
Azienda Unita Sanitaria Locale di Ravenna, Faenza, Italy
Romagnolo per lo Studio e la Cura dei Tumori IRST-IRCCS - Oncologia medica, Meldola (FC), Italy
Ospedale San Raffaele, Milan, Italy
Fondazione IRCCS National Cancer Institute, Milan, Italy
Istituto Nazionale Tumori- G. Pascale, Naples, Italy
Policlinico Universitario Agostino Gemelli, Roma, Italy
LLC "VitaMed", Moscow, Russia
State Budget-Funded Healthcare Institution of Novosibirsk Oblast "Novosibirsk Oblast Oncology Dispensary", Novosibirsk, Russia
Budget-Funded Healthcare Institution of Omsk Oblast "Clinical Oncology Dispensary", Omsk, Russia
State Budget Institution of Health "Leningrad Regional Oncologicacal Dispensary", Saint Petersburg, Russia
Oncology and Radiology Institute Serbia, Belgrade, Serbia
Oncology Institute Vojvodina, Kamenitz, Serbia
Clinical Centre Nis, Oncology Clinic, Niš, Serbia
ICO Hospital Germans Trias i Pujol, Badalona, Spain
Onkologikoa, Donostia / San Sebastian, Spain
Hospital Teresa Herrera (CHUACoruña), A Coruña, Spain
IOR - Hospital Quiron Dexeus, Barcelona, Spain
Hospital Vall D'Hebron, Barcelona, Spain
Institut Català d'Oncologia - Unitad de Investigación Clínica, Barcelona, Spain
Hospital Reina Sofia, Córdoba, Spain
Complejo Hospitalario Granada, Granada, Spain
Hospital Universitario Gregorio Maranon, Madrid, Spain
MD Anderson Cancer Center - Madrid, Madrid, Spain
Hospital Universitario Ramon Y Cajal, Madrid, Spain
Servicio de Oncología Médica Hospital Universitario La Paz, Madrid, Spain
Hospital Universitario HM Sanchinarro, Madrid, Spain
Hospital Regional Universitario Malaga - Hospital Materno Infantil de Málaga, Málaga, Spain
Hospital Son Llatzer (HSLL), Palma de Mallorca, Spain
Instituto Valenciano de Oncologia, Valencia, Spain
Kantonsspital Winterthur, Medizinische Onkologie, Winterthur, Switzerland
Kantonsspital, Winterthur, Switzerland
Hopitaux Universitaires de Geneve, Geneva, Switzerland
UCL Cancer Institute, London, United Kingdom
The Christie NHS Foundation Trust, Manchester, United Kingdom
Nottingham University Hospitals NHS Trust - City Hospital, Nottingham, United Kingdom
Lancashire Teaching Hospitals NHS Foundation Trust - Royal Preston Hospital, Preston, United Kingdom
The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital (RMH), Sutton, United Kingdom
The Royal Wolverhampton Hospitals NHS Trust - New Cross Hospital - GOW, Wolverhampton, United Kingdom
Peterborough City Hospital, Peterborough, United Kingdom
Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
Cancer,Haematology and Physics Directorate, Cancer Centre Royal Stoke University, Stoke-on-Trent, United Kingdom
University Hospitals Coventry & Warwickshire NHS Trust, Arden Cancer Centre, Coventry, United Kingdom
Mount Vernon Cancer Centre, Northwood, United Kingdom