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 (SORAYA)

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

This study is designed to evaluate the efficacy and safety of mirvetuximab soravtansine (MIRV) in patients 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). Patients will be, in the opinion of the Investigator, appropriate for single-agent therapy for their next line of therapy. All patients will receive single-agent MIRV at 6 mg/kg adjusted ideal body weight administered on Day 1 of every 3-week cycle.

Study Overview

• Status: Completed
• Conditions: Fallopian Tube Cancer; Epithelial Ovarian Cancer; Peritoneal Cancer
• Intervention / Treatment: Drug: Mirvetuximab Soravtansine

Detailed Description

This study is designed to evaluate the efficacy and safety of mirvetuximab soravtansine (MIRV) in patients 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). Patients 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 patients will be enrolled to achieve a total of 105 efficacy evaluable patients. Efficacy evaluable patients 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 patients 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).

Patients 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 patient's withdrawal of consent (whichever occurs first).

Patients 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 patients 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.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female patients ≥ 18 years of age
2. Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer

3. Patients must have platinum-resistant disease:

   1. Patients 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
   2. Patients 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: Patients who are platinum refractory during front-line treatment are excluded (see exclusion criteria)

4. Patients must have progressed radiographically on or after their most recent line of anticancer therapy.
5. Patients 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
6. Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1 Assay
7. Patients must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)

8. Patients 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:

   1. Adjuvant ± neoadjuvant considered 1 line of therapy
   2. 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)
   3. Therapy changed due to toxicity in the absence of progression will be considered part of the same line (i.e., not counted independently)
   4. Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
9. Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1

10. Patients must have completed prior therapy within the specified times below:

    1. Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to first dose of MIRV
    2. Focal radiation completed at least 2 weeks prior to first dose of MIRV
11. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia)
12. Patients 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

13. Patients must have adequate hematologic, liver and kidney functions defined as:

    1. 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
    2. Platelet count ≥ 100 x 10^9/L (100,000/μL) without platelet transfusion in the prior 10 days
    3. Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days
    4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
    5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
    6. Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN)
    7. Serum albumin ≥ 2 g/dL
14. Patients or their legally authorized representative must be willing and able to sign the informed consent form (ICF) and to adhere to the protocol requirements
15. Women of childbearing potential (WCBP) must agree to use highly effective contraceptive method(s) (as defined in Section 5.8.6 of the protocol) while on MIRV and for at least 3 months after the last dose
16. WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV

Exclusion Criteria:

1. Male patients
2. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/borderline ovarian tumor
3. Patients 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
4. Patients with prior wide-field radiotherapy (RT) affecting at least 20 percent of the bone marrow
5. Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
6. Patients 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

7. Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:

   1. Active hepatitis B or C infection (whether or not on active antiviral therapy)
   2. Human immunodeficiency virus (HIV) infection
   3. Active cytomegalovirus infection
   4. 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

8. Patients with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)

9. Patients with clinically significant cardiac disease including, but not limited to, any of the following:

   1. Myocardial infarction ≤ 6 months prior to first dose
   2. Unstable angina pectoris
   3. Uncontrolled congestive heart failure (New York Heart Association > class II)
   4. Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
   5. Uncontrolled cardiac arrhythmias
10. Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment
11. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
12. Patients with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
13. Patients requiring use of folate-containing supplements (eg, folate deficiency)
14. Patients with prior hypersensitivity to monoclonal antibodies (mAb)
15. Women who are pregnant or breastfeeding
16. Patients who received prior treatment with MIRV or other FRα-targeting agents
17. Patients with untreated or symptomatic central nervous system (CNS) metastases

18. Patients with a history of other malignancy within 3 years prior to enrollment.

    Note: patients 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

19. Prior known hypersensitivity reactions to study drugs and/or any of their excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; All patients 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.; Other Names: IMGN853; MIRV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate (ORR), which includes best response of complete response (CR) or partial response (PR) as assessed by the Investigator.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	The time from initial Investigator-assessed response (CR or PR) until progressive disease (PD) as assessed by the Investigator	Up to 2 years
Adverse Events (AEs)	Adverse Events (AE's) will be evaluated according to the NCI CTCAE v5.0. AE's will be coded using the latest Medical Dictionary for Regulatory Activities (MedDRA) version and summarized per system organ class (SOC) and preferred term (PT).	Up to 2 years
Progression-Free Survival (PFS)	The time from first dose of MIRV until Investigator-assessed radiological progressive disease (PD) or death, whichever occurs first.	Up to 2 years
Overall Survival (OS)	The time from first dose of MIRV until death.	Up to 2 years
CA-125 Response	Serum CA-125 response determined using the Gynecologic Cancer Intergroup (GCIG) criteria.	Up to 2 years

Collaborators and Investigators

• Sponsor: ImmunoGen, Inc.
• Investigators: Study Director: Michael Method, MPH, MBA, ImmunoGen, Inc.; Principal Investigator: Ursula Matulonis, MD, Dana-Farber Cancer Institute; Principal Investigator: Robert Coleman, MD, The US Oncology Network

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2020
• Primary Completion (Actual): November 16, 2021
• Study Completion (Actual): November 16, 2022

Study Registration Dates

• First Submitted: February 27, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Epithelial Ovarian Cancer; Phase 3; Platinum resistant; Peritoneal Cancer; Fallopian Tube Cancer; IMGN853; Folate-receptor alpha expression; Antibody-drug conjugate; mirvetuximab soravtansine; MIRV; FRα
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Immunoconjugates; Maytansine; Mirvetuximab soravtansine
• Other Study ID Numbers: IMGN853-0417; 2020-000179-19 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No