Study 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.

Condition or Disease	Intervention/Treatment
Epithelial Ovarian Cancer Peritoneal Cancer Fallopian Tube Cancer	Drug: Mirvetuximab Soravtansine

Study Design

Study Type	Interventional
Actual Enrollment	106 participants
Design Allocation	N/A
Interventional Model	Single Group Assignment
Masking	None (Open Label)
Primary Purpose	Treatment
Official Title	SORAYA: A Phase 3, Single Arm Study of Mirvetuximab Soravtansine in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression
Study Start Date	July 23, 2020
Actual Primary Completion Date	November 16, 2021
Actual Study Completion Date	November 16, 2022

Groups and Cohorts

Group/ Cohort	Intervention/ Treatment
Treatment 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).	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.

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.

Eligibility Criteria

Ages Eligible for Study	18 Years and Older (Adult, Older Adult)
Sexes Eligible for Study	Female
Accepts Healthy Volunteers	No
Inclusion Criteria	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
Exclusion Criteria	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) Women who are pregnant or breastfeeding Participants who received prior treatment with MIRV or other FRα-targeting agents 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

Contacts and Locations

Sponsors and Collaborators	ImmunoGen, Inc.
Locations	Arizona Oncology Associates | Phoenix, Arizona, United States, 85016 City of Hope Medical Center | Duarte, California, United States, 91010 California Cancer Associates (cCARE) | Fresno, California, United States, 93720 Stanford School of Medicine | Palo Alto, California, United States, 94394 California Pacific Medical Center Research Institute | San Francisco, California, United States, 94109 Rocky Mountain Cancer Centers | Littleton, Colorado, United States, 80120 Sarasota Memorial Health Care System | Sarasota, Florida, United States, 34239 Florida Cancer Specialists Panhandle | Tallahassee, Florida, United States, 32308 University of South Florida | Tampa, Florida, United States, 33606 Florida Cancer Specialists Research | West Palm Beach, Florida, United States, 33401 Northside Hospital | Atlanta, Georgia, United States, 30342 Hinsdale Hospital | Hinsdale, Illinois, United States, 60521 St. Vincent Gynecologic Oncology | Indianapolis, Indiana, United States, 46260 University of Kansas Cancer Center | Westwood, Kansas, United States, 66205 Norton Cancer Institute | Louisville, Kentucky, United States, 40207 Women's Cancer Center | Covington, Louisiana, United States, 70433 Maryland Oncology Hematology, P.A. | Rockville, Maryland, United States, 20850 Massachusetts General Hospital | Boston, Massachusetts, United States, 02114 Dana Farber Cancer Institute | Boston, Massachusetts, United States, 02215 Midwest Oncology Associates/Sarah Cannon | Kansas City, Missouri, United States, 64132 Center of Hope at Renown Medical Center | Reno, Nevada, United States, 89502 Holy Name Medical Center | Teaneck, New Jersey, United States, 07666 Mount Sinai Health System | New York, New York, United States, 10029 Memorial Sloan-Kettering Cancer Center | New York, New York, United States, 10065 Sarah Cannon Research Institute / Tennessee Oncology, PLLC | Nashville, Tennessee, United States, 37203 Texas Oncology-Austin Central | Austin, Texas, United States, 78731 Texas Oncology, P.A. - Fort Worth Cancer Center | Fort Worth, Texas, United States, 76104 Texas Oncology, P.A. - McAllen | McAllen, Texas, United States, 78503 Texas Oncology, P.A. - Sugar Land | Sugar Land, Texas, United States, 77479 USOR: Texas Oncology - The Woodlands, Gynecologic Oncology | The Woodlands, Texas, United States, 77380 Texas Oncology, P.A. - Tyler | Tyler, Texas, United States, 75702 Kadlec Clinic Hematology and Oncology | Kennewick, Washington, United States, 99336 University of Wisconsin Carbone Cancer Center | Madison, Wisconsin, United States, 53792 Froedtert and the Medical College of Wisconsin Department of Obstetrics & Gynecology | Milwaukee, Wisconsin, United States, 53226 Royal North Shore Hospital | St. Leonards, New South Wales, Australia, 2065 ICON Cancer Care | Auchenflower, Queensland, Australia, 4066 Peninsula and South Eastern Haematology & Oncology Group | Frankston, Victoria, Australia, 3199 St John of God Subiaco Hospital | Subiaco, Western Australia, Australia, 6008 Cliniques Universitaires Saint Luc - lnstitut Roi Albert II | Brussels, Bruxelles, Belgium, 1200 Centre Hopsitalier de l'Ardenne | Libramont, Luxembourg, Belgium, 6800 UZ Gent | Gent, Belgium, 9000 UZ Leuven | Leuven, Belgium, 3000 CHU UCL Namur/Site Sainte Elisabeth | Namur, Belgium, B5000 MHAT "Serdika" | Sofia, Bulgaria, 1632 Všeobecná fakultní nemocnice v Praze | Praha 2, Prague, Czechia, 128 51 Universitätsmedizin Mannheim | Mannheim, Baden-Württemberg, Germany, 68167 UMG Frauenklinik Robert-Koch-Str. 40 | Göttingen, Niedersachsen, Germany, 37075 KEM | Essen, Germany, 45135 Mater Misericordiae University Hospital | Dublin, Leinster, Ireland, 7 St. James's Hospital | Dublin, Leinster, Ireland, 8 Cork University Hospital | Cork, Munster, Ireland, T12 DC4A Bon Secours Hospital | Cork, Munster, Ireland, T12 DV56 University Hospital Waterford | Waterford, Munster, Ireland, X91ER8E Beaumont Hospital | Dublin, Ireland, 9 Rambam Medical Center | Haifa, Israel, PO Box 9601 Shaare Zedek Medical Center | Jerusalem, Israel, 91031 Hadassah Ein Kerem Medical center | Jerusalem, Israel, POB 12000 Meir Medical Center | Kfar Saba, Israel, 4428164 Sheba Medical Center | Ramat Gan, Israel, 5265601 Kaplan Medical Center | Rehovot, Israel, 76100 Ziv Medical Center | Safed, Israel, 13100 Policlinico S. Orsola-Malpighi | Bologna, Italy, 40138 Azienda Socio Santaria Territoriale degli Spedali Civili di Brescia | Brescia, Italy, 25123 Istituto Oncologico Candiolo | Candiolo, Italy, 10060 Ospedale Cannizzaro di Catania | Catania, Italy, 95126 IEO Istituto Europeo di Oncologia | Milano, Italy, 20141 Azienda Ospedaliera Ospedale Niguarda Ca'Granda | Milano, Italy, 20162 Fondazione IRCCS Istituto Nazionale dei Tumori | Napoli, Italy, 80131 Istituto Nazionale Tumori- G. Pascale | Napoli, Italy, 87100 Ospedale S.Maria della Misericordia | Perugia, Italy, 6129 Fondazione Policlinico Universitario A. Gemelli IRCCS | Roma, Italy, 00168 Specjalistyczna Przychodnia Lekarska Medicus | Chorzów, Silesia, Poland, 41-500 Mazurskim Centrum Onkologiiw Olsztynie | Olsztyn, Warmińsko-Mazurskie, Poland, 10-228 Instytut Centrum Zdrowia Matki Polki | Łódź, Łódzkie, Poland, 93-338 Institut Català d'Oncologia Badalona Hospital Universitari Germans Trias i Pujol | Badalona, Barcelona, Spain, 08916 Hospital La Paz | Madrid, Castellana, Spain, 28046 Hospital Teresa Herrera - Complejo Hospitalario Universitario A Coruna | A Coruña, Galicia, Spain, 15006 Hospital Quirón Dexeus | Barcelona, Spain, 08028 Vall d'Hebron Institute of Oncology | Barcelona, Spain, 08035 lnstitut Catala d' Oncologia L' Hospitalet | Barcelona, Spain, 08908 Hospital Reina Sofia de Cordoba | Córdoba, Spain, 14004 Institut Català d'Oncología de Girona | Girona, Spain, 17007 Clinica Universidad de Navarra | Madrid, Spain, 28027 MD Anderson Cancer Centre | Madrid, Spain, 28033 Hospital Clínico Universitario San Carlos | Madrid, Spain, 28040 Hospital Clinico Universitario Virgen de la Arrixaca | Murcia, Spain, 30120 Corporació Sanitaria Parc Taulí | Sabadell, Spain, 08208 Hospital Clinico Universitario de Valencia | Valencia, Spain, 46010 Instituto Valenciano de Oncologia | Valencia, Spain, 46010
Investigators	Principal Investigator: Ursula Matulonis, MD, Dana-Farber Cancer Institute Principal Investigator: Robert Coleman, MD, The US Oncology Network

Study Documents (Full Text)

• Documents Provided by ImmunoGen, Inc.: Study Protocol August 28, 2020
• Documents Provided by ImmunoGen, Inc.: Statistical Analysis Plan November 5, 2021

More Information

Additional Relevant MeSH Terms

• Ovarian Neoplasms
• Carcinoma, Ovarian Epithelial
• Fallopian Tube Neoplasms
• Endocrine Gland Neoplasms
• Neoplasms by Site
• Neoplasms
• Ovarian Diseases
• Adnexal Diseases
• Genital Diseases, Female
• Female Urogenital Diseases
• Female Urogenital Diseases and Pregnancy Complications
• Urogenital Diseases
• Genital Neoplasms, Female
• Urogenital Neoplasms
• Genital Diseases
• Endocrine System Diseases
• Gonadal Disorders
• Carcinoma
• Neoplasms, Glandular and Epithelial
• Neoplasms by Histologic Type
• Fallopian Tube Diseases