Clinical trial NCT04296890: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Epithelial Ovarian Cancer
Peritoneal Cancer
Fallopian Tube Cancer
Keywords: Platinum resistant
Folate-receptor alpha expression
Phase 3
Antibody-drug conjugate
mirvetuximab soravtansine
IMGN853
Epithelial Ovarian Cancer
Peritoneal Cancer
Fallopian Tube Cancer
MIRV
FRα
Lead sponsor: ImmunoGen, Inc.
Sponsor class: INDUSTRY
First posted: 2020-03-05
Enrollment: 106
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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)
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Female participants ≥ 18 years of age
2. Participants must have a confirmed diagnosis of high-grade serous epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer
3. Participants must have platinum-resistant disease:

   1. 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
   2. 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)
4. Participants must have progressed radiographically on or after their most recent line of anticancer therapy.
5. 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
6. Participant's tumor must be positive for FRα expression as defined by the Ventana FOLR1 Assay
7. Participants must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)
8. 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:

   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. Participants must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
10. Participants 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. Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia)
12. 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
13. Participants 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. 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
15. 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
16. WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV

Exclusion Criteria:

1. Male participants
2. Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/borderline ovarian tumor
3. 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
4. Participants with prior wide-field radiotherapy (RT) affecting at least 20 percent of the bone marrow
5. Participants with \> Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
6. 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
7. Participants 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. Participants with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
9. Participants 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. Participants with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment
11. Participants with a history of cirrhotic liver disease (Child-Pugh Class B or C)
12. Participants with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
13. Participants requiring use of folate-containing supplements (eg, folate deficiency)
14. Participants with prior hypersensitivity to monoclonal antibodies (mAb)
15. Women who are pregnant or breastfeeding
16. Participants who received prior treatment with MIRV or other FRα-targeting agents
17. Participants with untreated or symptomatic central nervous system (CNS) metastases
18. 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
19. Prior known hypersensitivity reactions to study drugs and/or any of their excipients

Primary outcomes:
measure: 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)
timeFrame: Up to approximately 15 months
Secondary outcomes:
measure: Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1
timeFrame: Up to approximately 15 months
measure: Percentage of Participants With CA-125 Confirmed Clinical Response Per Gynecologic Cancer Intergroup (GCIG) Criteria
timeFrame: Up to approximately 15 months
measure: Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1
timeFrame: Up to approximately 15 months
measure: Overall Survival Assessed by the Investigator Using RECIST v1.1
timeFrame: Up to approximately 27 months
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 27 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Fresno
country: United States
facility: California Cancer Associates (cCARE)
state: California
city: Palo Alto
country: United States
facility: Stanford School of Medicine
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center Research Institute
state: California
city: Littleton
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Sarasota
country: United States
facility: Sarasota Memorial Health Care System
state: Florida
city: Tallahassee
country: United States
facility: Florida Cancer Specialists Panhandle
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists Research
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Hinsdale
country: United States
facility: Hinsdale Hospital
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Gynecologic Oncology
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Covington
country: United States
facility: Women's Cancer Center
state: Louisiana
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A.
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: Kansas City
country: United States
facility: Midwest Oncology Associates/Sarah Cannon
state: Missouri
city: Reno
country: United States
facility: Center of Hope at Renown Medical Center
state: Nevada
city: Teaneck
country: United States
facility: Holy Name Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Health System
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute / Tennessee Oncology, PLLC
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology-Austin Central
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology, P.A. - Fort Worth Cancer Center
state: Texas
city: McAllen
country: United States
facility: Texas Oncology, P.A. - McAllen
state: Texas
city: Sugar Land
country: United States
facility: Texas Oncology, P.A. - Sugar Land
state: Texas
city: The Woodlands
country: United States
facility: USOR: Texas Oncology - The Woodlands, Gynecologic Oncology
state: Texas
city: Tyler
country: United States
facility: Texas Oncology, P.A. - Tyler
state: Texas
city: Kennewick
country: United States
facility: Kadlec Clinic Hematology and Oncology
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin Department of Obstetrics & Gynecology
state: Wisconsin
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: ICON Cancer Care
state: Queensland
city: Frankston
country: Australia
facility: Peninsula and South Eastern Haematology & Oncology Group
state: Victoria
city: Subiaco
country: Australia
facility: St John of God Subiaco Hospital
state: Western Australia
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint Luc - lnstitut Roi Albert II
state: Bruxelles
city: Libramont
country: Belgium
facility: Centre Hopsitalier de l'Ardenne
state: Luxembourg
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Namur
country: Belgium
facility: CHU UCL Namur/Site Sainte Elisabeth
city: Sofia
country: Bulgaria
facility: MHAT "Serdika"
city: Praha 2
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze
state: Prague
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
state: Baden-Württemberg
city: Göttingen
country: Germany
facility: UMG Frauenklinik Robert-Koch-Str. 40
state: Niedersachsen
city: Essen
country: Germany
facility: KEM
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
state: Leinster
city: Dublin
country: Ireland
facility: St. James's Hospital
state: Leinster
city: Cork
country: Ireland
facility: Cork University Hospital
state: Munster
city: Cork
country: Ireland
facility: Bon Secours Hospital
state: Munster
city: Waterford
country: Ireland
facility: University Hospital Waterford
state: Munster
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Ein Kerem Medical center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Safed
country: Israel
facility: Ziv Medical Center
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi
city: Brescia
country: Italy
facility: Azienda Socio Santaria Territoriale degli Spedali Civili di Brescia
city: Candiolo
country: Italy
facility: Istituto Oncologico Candiolo
city: Catania
country: Italy
facility: Ospedale Cannizzaro di Catania
city: Milano
country: Italy
facility: IEO Istituto Europeo di Oncologia
city: Milano
country: Italy
facility: Azienda Ospedaliera Ospedale Niguarda Ca'Granda
city: Napoli
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori- G. Pascale
city: Perugia
country: Italy
facility: Ospedale S.Maria della Misericordia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS
city: Chorzów
country: Poland
facility: Specjalistyczna Przychodnia Lekarska Medicus
state: Silesia
city: Olsztyn
country: Poland
facility: Mazurskim Centrum Onkologiiw Olsztynie
state: Warmińsko-Mazurskie
city: Łódź
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
state: Łódzkie
city: Badalona
country: Spain
facility: Institut Català d'Oncologia Badalona Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Madrid
country: Spain
facility: Hospital La Paz
state: Castellana
city: A Coruña
country: Spain
facility: Hospital Teresa Herrera - Complejo Hospitalario Universitario A Coruna
state: Galicia
city: Barcelona
country: Spain
facility: Hospital Quirón Dexeus
city: Barcelona
country: Spain
facility: Vall d'Hebron Institute of Oncology
city: Barcelona
country: Spain
facility: lnstitut Catala d' Oncologia L' Hospitalet
city: Córdoba
country: Spain
facility: Hospital Reina Sofia de Cordoba
city: Girona
country: Spain
facility: Institut Català d'Oncología de Girona
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: MD Anderson Cancer Centre
city: Madrid
country: Spain
facility: Hospital Clínico Universitario San Carlos
city: Murcia
country: Spain
facility: Hospital Clinico Universitario Virgen de la Arrixaca
city: Sabadell
country: Spain
facility: Corporació Sanitaria Parc Taulí
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
Study officials:
affiliation: ImmunoGen, Inc.
name: Michael Method, MD, MPH, MBA
role: STUDY_DIRECTOR
affiliation: Dana-Farber Cancer Institute
name: Ursula Matulonis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The US Oncology Network
name: Robert Coleman, MD
role: PRINCIPAL_INVESTIGATOR
References: