A Study of Mirvetuximab Soravtansine in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression
- Conditions
- Peritoneal CancerEpithelial Ovarian CancerFallopian Tube Cancer
- Interventions
- Registration Number
- NCT04296890
- Lead Sponsor
- ImmunoGen, Inc.
- Brief Summary
This study is designed to evaluate the efficacy and safety of mirvetuximab soravtansine (MIRV) in participants with platinum-resistant high-grade serous epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of Folate Receptor-Alpha (FRα). Participants will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. All participants will receive single-agent MIRV at 6 mg/kg adjusted ideal body weight administered on Day 1 of every 3-week cycle.
- Detailed Description
This study is designed to evaluate the efficacy and safety of mirvetuximab soravtansine (MIRV) in participants with platinum-resistant high-grade serous epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose tumors express a high-level of Folate Receptor Alpha (FRα). Participants will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. FRα positivity will be defined by the Ventana FOLR1 (Folate Receptor 1/Folate Receptor Alpha) Assay.
Approximately 110 eligible participants will be enrolled to achieve a total of 105 efficacy evaluable participants. Efficacy evaluable participants include those who have measurable lesions per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) at baseline and received at least 1 dose of MIRV.
All participants will receive single-agent MIRV at 6 mg/kg adjusted ideal body weight (AIBW) administered on Day 1 of every 3-week cycle (Q3W).
Tumor response will be evaluated by the Investigator using RECIST v1.1. Computerized tomography (CT) or magnetic resonance imaging (MRI) scans will be collected for sensitivity analysis by blinded independent central review (BICR).
Participants will continue to receive MIRV until disease progression, unacceptable toxicity, withdrawal of consent, death, or until the Sponsor terminates the study (whichever comes first).
Tumor assessments, including radiological assessments by CT/MRI scans will be performed at Screening and subsequently every 6 weeks (± 1 week) from Cycle 1 Day 1 (C1D1) for the first 36 weeks then every 12 weeks (± 3 weeks) until disease progression, death, the start of new anticancer therapy, or participant's withdrawal of consent (whichever occurs first).
Participants who discontinue MIRV for reasons other than progressive disease (PD) will continue with tumor assessments until documentation of PD or the start of a new anticancer therapy, whichever comes first. Prior to Week 36 (from Cycle 1, Day 1), assessments should occur every 6 weeks (± 1 week) as allowed by local requirements but must occur at an interval of no more than 12 weeks. After Week 36, assessment will occur every 12 weeks (± 3 weeks) until documentation of PD or the start of new anticancer therapy.
All participants who discontinue MIRV will be followed for survival every 3 months (± 1 month) until death, lost to follow-up, withdrawal of consent for survival follow-up, or end of study (EOS) (whichever comes first). Additional survival follow-up calls may occur periodically, if needed.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 106
-
Female participants ≥ 18 years of age
-
Participants must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer
-
Participants must have platinum-resistant disease:
- Participants who have only had 1 line of platinum based therapy must have received at least 4 cycles of platinum, must have had a response (complete response/remission [CR] or partial response/remission [PR]) and then progressed between > 3 months and ≤ 6 months after the date of the last dose of platinum
- Participants 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: Participants who are platinum refractory during front-line treatment are excluded (see exclusion criteria)
-
Participants must have progressed radiographically on or after their most recent line of anticancer therapy.
-
Participants 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 immunohistochemistry (IHC) confirmation of Folate Receptor α (FRα) positivity
-
Participant's tumor must be positive for FRα expression as defined by the Ventana FOLR1 Assay
-
Participants must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)
-
Participants must have received at least 1 but no more than 3 prior systemic lines of anticancer therapy, including at least 1 line of therapy containing bevacizumab, and for whom single-agent therapy is appropriate as the next line of treatment:
- Adjuvant ± neoadjuvant considered 1 line of therapy
- Maintenance therapy (e.g., bevacizumab, poly adenosine diphosphate-ribose polymerase (PARP) inhibitors) will be considered part of the preceding line of therapy (i.e., not counted independently)
- Therapy changed due to toxicity in the absence of progression will be considered part of the same line (i.e., not counted independently)
- Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
-
Participants must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
-
Participants must have completed prior therapy within the specified times below:
- Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to first dose of MIRV
- Focal radiation completed at least 2 weeks prior to first dose of MIRV
-
Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia)
-
Participants must have completed any major surgery at least 4 weeks prior to first dose of MIRV and have recovered or stabilized from the side effects of prior surgery
-
Participants 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
-
Participants 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) while on MIRV and for at least 3 months after the last dose
-
WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV
-
Male participants
-
Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/borderline ovarian tumor
-
Participants 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
-
Participants with prior wide-field radiotherapy (RT) affecting at least 20 percent of the bone marrow
-
Participants with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
-
Participants 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
-
Participants 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)
- Human immunodeficiency virus (HIV) infection
- Active cytomegalovirus infection
- Any other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to the first dose of MIRV
Note: Testing at screening is not required for the above infections unless clinically indicated
-
Participants with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
-
Participants with clinically significant cardiac disease including, but not limited to, any 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
-
Participants with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment
-
Participants with a history of cirrhotic liver disease (Child-Pugh Class B or C)
-
Participants with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
-
Participants requiring use of folate-containing supplements (eg, folate deficiency)
-
Participants with prior hypersensitivity to monoclonal antibodies (mAb)
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Women who are pregnant or breastfeeding
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Participants who received prior treatment with MIRV or other FRα-targeting agents
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Participants with untreated or symptomatic central nervous system (CNS) metastases
-
Participants with a history of other malignancy within 3 years prior to enrollment.
Note: Participants with 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) are eligible
-
Prior known hypersensitivity reactions to study drugs and/or any of their excipients
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Mirvetuximab Soravtansine All participants will receive single-agent mirvetuximab soravtansine (MIRV) at 6 mg/kg adjusted ideal body weight (AIBW) administered on Day 1 of every 3-week cycle (Q3W).
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Up to approximately 15 months ORR was defined as percentage of participants with a confirmed 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 \<10 millimeters (mm). PR: At least 30% decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 Up to approximately 15 months DOR was defined as the time from the date of the first response (CR or PR), until the date of progressive disease (PD) or death from any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. 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 estimated using the Kaplan-Meier method.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Up to approximately 27 months An adverse event (AE) was defined as 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. TEAEs were defined as AEs with an onset date on or after the first dose of Study drug, and within 30 days of the last dose of study drug or prior to the start of a new anticancer treatment, whichever occurred first. A summary of all Serious Adverse Events (SAEs) and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Percentage of Participants With CA-125 Confirmed Clinical Response Per Gynecologic Cancer Intergroup (GCIG) Criteria Up to approximately 15 months The GCIG CA-125 response was defined as at least 50% reduction in CA-125 levels from baseline. The response must have been confirmed and maintained for at least 28 days.
Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 Up to approximately 15 months PFS was defined as the time from initiation of study drug until the date of 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.
Overall Survival Assessed by the Investigator Using RECIST v1.1 Up to approximately 27 months Overall survival was defined as the time from the date of first dose until the date of death from any cause, estimated using the Kaplan-Meier method.
Trial Locations
- Locations (89)
St. Vincent Gynecologic Oncology
🇺🇸Indianapolis, Indiana, United States
St John of God Subiaco Hospital
🇦🇺Subiaco, Western Australia, Australia
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Arizona Oncology Associates
🇺🇸Phoenix, Arizona, United States
California Pacific Medical Center Research Institute
🇺🇸San Francisco, California, United States
Azienda Socio Santaria Territoriale degli Spedali Civili di Brescia
🇮🇹Brescia, Italy
Istituto Oncologico Candiolo
🇮🇹Candiolo, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Napoli, Italy
Fondazione Policlinico Universitario A. Gemelli IRCCS
🇮🇹Roma, Italy
Froedtert and the Medical College of Wisconsin Department of Obstetrics & Gynecology
🇺🇸Milwaukee, Wisconsin, United States
MD Anderson Cancer Centre
🇪🇸Madrid, Spain
City of Hope Medical Center
🇺🇸Duarte, California, United States
California Cancer Associates (cCARE)
🇺🇸Fresno, California, United States
Stanford School of Medicine
🇺🇸Palo Alto, California, United States
Sarasota Memorial Health Care System
🇺🇸Sarasota, Florida, United States
Northside Hospital
🇺🇸Atlanta, Georgia, United States
Florida Cancer Specialists Research
🇺🇸West Palm Beach, Florida, United States
Hinsdale Hospital
🇺🇸Hinsdale, Illinois, United States
Maryland Oncology Hematology, P.A.
🇺🇸Rockville, Maryland, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Midwest Oncology Associates/Sarah Cannon
🇺🇸Kansas City, Missouri, United States
Mount Sinai Health System
🇺🇸New York, New York, United States
Sarah Cannon Research Institute / Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Texas Oncology-Austin Central
🇺🇸Austin, Texas, United States
Texas Oncology, P.A. - Sugar Land
🇺🇸Sugar Land, Texas, United States
Texas Oncology, P.A. - McAllen
🇺🇸McAllen, Texas, United States
Texas Oncology, P.A. - Fort Worth Cancer Center
🇺🇸Fort Worth, Texas, United States
USOR: Texas Oncology - The Woodlands, Gynecologic Oncology
🇺🇸The Woodlands, Texas, United States
Texas Oncology, P.A. - Tyler
🇺🇸Tyler, Texas, United States
Kadlec Clinic Hematology and Oncology
🇺🇸Kennewick, Washington, United States
University of Wisconsin Carbone Cancer Center
🇺🇸Madison, Wisconsin, United States
Royal North Shore Hospital
🇦🇺St. Leonards, New South Wales, Australia
ICON Cancer Care
🇦🇺Auchenflower, Queensland, Australia
Centre Hopsitalier de l'Ardenne
🇧🇪Libramont, Luxembourg, Belgium
Cliniques Universitaires Saint Luc - lnstitut Roi Albert II
🇧🇪Brussels, Bruxelles, Belgium
UZ Gent
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
MHAT "Serdika"
🇧🇬Sofia, Bulgaria
Všeobecná fakultní nemocnice v Praze
🇨🇿Praha 2, Prague, Czechia
UMG Frauenklinik Robert-Koch-Str. 40
🇩🇪Göttingen, Niedersachsen, Germany
KEM
🇩🇪Essen, Germany
Mater Misericordiae University Hospital
🇮🇪Dublin, Leinster, Ireland
St. James's Hospital
🇮🇪Dublin, Leinster, Ireland
Cork University Hospital
🇮🇪Cork, Munster, Ireland
Beaumont Hospital
🇮🇪Dublin, Ireland
Rambam Medical Center
🇮🇱Haifa, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Hadassah Ein Kerem Medical center
🇮🇱Jerusalem, Israel
Meir Medical Center
🇮🇱Kfar Saba, Israel
Kaplan Medical Center
🇮🇱Rehovot, Israel
Policlinico S. Orsola-Malpighi
🇮🇹Bologna, Italy
Ziv Medical Center
🇮🇱Safed, Israel
Ospedale Cannizzaro di Catania
🇮🇹Catania, Italy
Azienda Ospedaliera Ospedale Niguarda Ca'Granda
🇮🇹Milano, Italy
IEO Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Ospedale S.Maria della Misericordia
🇮🇹Perugia, Italy
Istituto Nazionale Tumori- G. Pascale
🇮🇹Napoli, Italy
Mazurskim Centrum Onkologiiw Olsztynie
🇵🇱Olsztyn, Warmińsko-Mazurskie, Poland
Hospital La Paz
🇪🇸Madrid, Castellana, Spain
Hospital Teresa Herrera - Complejo Hospitalario Universitario A Coruna
🇪🇸A Coruña, Galicia, Spain
Institut Català d'Oncologia Badalona Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Quirón Dexeus
🇪🇸Barcelona, Spain
Vall d'Hebron Institute of Oncology
🇪🇸Barcelona, Spain
Institut Català d'Oncología de Girona
🇪🇸Girona, Spain
lnstitut Catala d' Oncologia L' Hospitalet
🇪🇸Barcelona, Spain
Hospital Reina Sofia de Cordoba
🇪🇸Córdoba, Spain
Clinica Universidad de Navarra
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Clínico Universitario San Carlos
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
Corporació Sanitaria Parc Taulí
🇪🇸Sabadell, Spain
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Florida Cancer Specialists Panhandle
🇺🇸Tallahassee, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Bon Secours Hospital
🇮🇪Cork, Munster, Ireland
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Peninsula and South Eastern Haematology & Oncology Group
🇦🇺Frankston, Victoria, Australia
Instytut Centrum Zdrowia Matki Polki
🇵🇱Łódź, Łódzkie, Poland
Rocky Mountain Cancer Centers
🇺🇸Littleton, Colorado, United States
Specjalistyczna Przychodnia Lekarska Medicus
🇵🇱Chorzów, Silesia, Poland
CHU UCL Namur/Site Sainte Elisabeth
🇧🇪Namur, Belgium
Women's Cancer Center
🇺🇸Covington, Louisiana, United States
Universitätsmedizin Mannheim
🇩🇪Mannheim, Baden-Württemberg, Germany
University Hospital Waterford
🇮🇪Waterford, Munster, Ireland
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Center of Hope at Renown Medical Center
🇺🇸Reno, Nevada, United States
Holy Name Medical Center
🇺🇸Teaneck, New Jersey, United States