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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04209855




Registration number
NCT04209855
Ethics application status
Date submitted
17/12/2019
Date registered
24/12/2019
Date last updated
6/05/2021

Titles & IDs
Public title
A Study of Mirvetuximab Soravtansine vs. Investigator's Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression
Scientific title
MIRASOL: A Randomized, Open-label, Phase 3 Study of Mirvetuximab Soravtansine vs. Investigator's Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression
Secondary ID [1] 0 0
2019-003509-80
Secondary ID [2] 0 0
IMGN853-0416
Universal Trial Number (UTN)
Trial acronym
MIRASOL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Epithelial Ovarian Cancer 0 0
Peritoneal Cancer 0 0
Fallopian Tube Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mirvetuximab Soravtansine
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Topotecan
Treatment: Drugs - Pegylated liposomal doxorubicin

Experimental: mirvetuximab soravtansine (MIRV; IMGN853) - MIRV 6 mg/kg adjusted ideal body weight (AIBW) every 3 weeks (Q3W)

Active Comparator: Investigator's choice of chemotherapy - Paclitaxel (Pac; 80 mg/m2) administered once per week (QW) within a 4-week cycle
Pegylated liposomal doxorubicin (PLD; 40 mg/m2) administered every 4 weeks (Q4W)
Topotecan (Topo; 4 mg/m2) administered either on Days 1, 8, and 15 every 4 weeks or for 5 consecutive days (1.25 mg/m2 Days 1-5) every 3 weeks (Q3W)


Treatment: Drugs: Mirvetuximab Soravtansine
Mirvetuximab soravtansine is an antibody drug conjugate designed to target folate receptor a (FRa). It consists of the humanized anti-FRa mAb M9346A attached via a cleavable disulfide linker to the cytotoxic maytansinoid, DM4.

Treatment: Drugs: Paclitaxel
Paclitaxel is a taxane that can stabilize microtubules to inhibit cell division. It was approved for treatment of recurrent epithelial ovarian cancer.

Treatment: Drugs: Topotecan
Topotecan induces irreversible DNA damage. It inhibits topoisomerase 1, leading to both single and double strand DNA break that eventually promote apoptosis. Topotecan was approved for treatment of epithelial ovarian cancer after failure of initial or subsequent chemotherapy.

Treatment: Drugs: Pegylated liposomal doxorubicin
Pegylated liposomal doxorubicin is a standard chemotherapy regimen used for treating platinum-resistant ovarian cancer. The active component doxorubicin is an anthracycline that intercalates DNA, leading to inhibition of replication and subsequently, the inhibition of proper cell division.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) - The time from date of randomization until Investigator-assessed progressive disease or death, whichever occurs first.
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [1] 0 0
Safety and tolerability - Adverse events (AEs) will be evaluated according to the NCI CTCAE v5.0. AEs will be coded using the latest Medical Dictionary for Regulatory Activities (MedDRA) version and summarized per system organ class (SOC) and preferred term (PT).
Timepoint [1] 0 0
Up to 2 years
Secondary outcome [2] 0 0
Objective Response Rate (ORR) - Objective response includes best response of complete response (CR) or partial response (PR).
Timepoint [2] 0 0
Up to 2 years
Secondary outcome [3] 0 0
Overall survival - The time from date of randomization until the date of death
Timepoint [3] 0 0
Up to 2 years
Secondary outcome [4] 0 0
Primary patient-reported outcomes - The number of patients achieving at least 15 point absolute improvement at Week 8 or Week 9 in the abdominal/GI scale of the European Organization for Research and Treatment of Cancer (EORTC) ovarian cancer specific quality of life questionnaire (QLQ-OV28). A higher score represents a better quality of life.
Timepoint [4] 0 0
Up to 2 years
Secondary outcome [5] 0 0
Duration of response (DOR) - The time from initial response until Investigator-assessed progressive disease for all patients who achieve a confirmed objective response
Timepoint [5] 0 0
Up to 2 years
Secondary outcome [6] 0 0
CA-125 response - Serum CA-125 response determined using the GCIG criteria
Timepoint [6] 0 0
Up to 2 years
Secondary outcome [7] 0 0
Progression-free survival 2 (PFS 2) - The time from date of randomization until second disease progression or death whichever occurs first. Results will be summarized by arm
Timepoint [7] 0 0
Up to 2 years

Eligibility
Key inclusion criteria
1. Female patients = 18 years of age

2. Patients must have a confirmed diagnosis of high-grade serous epithelial ovarian
cancer, primary peritoneal cancer, or fallopian tube cancer

3. Patients must have platinum-resistant disease (defined as progression within 6 months
from completion of a minimum of four cycles of platinum-containing therapy) Note: This
should be calculated from the date of the last administered dose of platinum therapy
to the date of the radiographic imaging showing progression. Patients who are
platinum-refractory during front-line treatment are excluded

4. Patients must have progressed on or after their most recent line of therapy Note:
Progression must be determined radiographically and/or by CA-125 GCIG progression
criteria

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 IHC confirmation of FRa positivity

6. Patient's tumor must be positive for FRa expression as defined by the Ventana FOLR1
(FOLR-2.1) CDx assay

7. Patients must have at least one 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, and for whom single-agent therapy is appropriate as the next line
of treatment:

1. Adjuvant ± neoadjuvant considered one line of therapy

2. Maintenance therapy (eg, bevacizumab, PARP inhibitors) will be considered as part
of the preceding line of therapy (ie, not counted independently)

3. Therapy changed due to toxicity in the absence of progression will be considered
as part of the same line (ie, not counted independently)

4. Hormonal therapy will be counted as a separate line of therapy unless it was
given as maintenance

9. Patient must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS)
of 0 or 1

10. Time from prior therapy:

1. Systemic antineoplastic therapy (5 half-lives or 4 weeks, whichever is shorter)

2. Focal radiation completed at least 2 weeks prior to first dose of study drug

11. Patients must have stabilized or recovered (Grade 1 or baseline) from all prior
therapy-related toxicities

12. Major surgery must be completed at least 4 weeks prior to first dose 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 109/L (1,500/µL)

2. Platelet count = 100 x 109/L (100,000/µL) without platelet transfusion in the
prior 10 days

3. Hemoglobin = 9.0 g/dL

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 5.9.6 in the protocol) while on study
drug and for at least 3 months after the last dose of MIRV or at least 6 months after
the last dose of paclitaxel, pegylated liposomal doxorubicin, or topotecan

16. WCBP must have a negative pregnancy test within 4 days prior to the first dose of
study drug
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed
tumors containing any of the above histologies, or low-grade or borderline ovarian
tumor

2. Patients with primary platinum-refractory disease, defined as disease that did not
respond to or has progressed within 3 months of the last dose of first line
platinum-containing chemotherapy

3. Patients with prior wide-field RT affecting at least 20% of the bone marrow

4. Patients with > Grade 1 peripheral neuropathy per CTCAE v5.0

5. 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

6. 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. HIV infection

3. Cytomegalovirus infection

4. Any other concurrent infectious disease requiring IV antibiotics within 2 weeks
before starting study drug

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

8. Patients with clinically significant cardiac disease including, but not limited to,
any one 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

9. Patients assigned to PLD stratum only: Left ventricular ejection fraction (LVEF) below
the institutional limit of normal as measured by echocardiography (ECHO) or multigated
acquisition (MUGA) scan

10. Patients with a history of hemorrhagic or ischemic stroke within six months prior to
randomization

11. Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)

12. Patients with a previous clinical diagnosis of non-infectious interstitial lung
disease (ILD), including noninfectious pneumonitis

13. Patients with required use of folate-containing supplements (eg, folate deficiency)

14. Patients with prior hypersensitivity to monoclonal antibodies

15. Women who are pregnant or lactating

16. Patients with prior treatment with MIRV or other FRa-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 randomization.
Note: does not include 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Newcastle Private Hospital - New Lambton Heights
Recruitment hospital [2] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Oncology Clinics Victoria (OCV) - Cabrini Malvern Hospital Location - Malvern
Recruitment hospital [5] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [6] 0 0
Burnside War Memorial Hospital - The Brian Fricker Oncology Centre - Toorak Gardens
Recruitment postcode(s) [1] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3144 - Malvern
Recruitment postcode(s) [5] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [6] 0 0
5065 - Toorak Gardens
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
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Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
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Illinois
Country [10] 0 0
United States of America
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Indiana
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
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Louisiana
Country [13] 0 0
United States of America
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Maryland
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United States of America
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Massachusetts
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United States of America
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Michigan
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Minnesota
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Missouri
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Montana
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United States of America
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Nevada
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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Tennessee
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Texas
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United States of America
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Virginia
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Washington
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United States of America
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West Virginia
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Belgium
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Brasschaat
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Belgium
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Leuven
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Canada
State/province [35] 0 0
Alberta
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Canada
State/province [36] 0 0
Ontario
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Canada
State/province [37] 0 0
Quebec
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Czechia
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Ostrava
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Czechia
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Praha 2
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Czechia
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Zlín
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France
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Cedex 9
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France
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Cedex B.P 307
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France
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Cedex
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France
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Besançon Cedex
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Bordeaux Cedex
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Lyon Cedex
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Paris
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France
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Pierre-Bénite
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France
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Plerin
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France
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Saint Cloud
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France
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St. Herblain CEDEX
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France
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Vandoeuvre les Nancy_ Cedex
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France
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Villejuif Cedex
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Germany
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Hamburg
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Israel
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Jerusalem
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Israel
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Kfar Saba
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Italy
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Brescia
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Italy
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Milan
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Italy
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Reggio Emilia
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Italy
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Torino
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Seongnam-si
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Korea, Republic of
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Seoul
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Netherlands
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Amsterdam
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Netherlands
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Maastricht
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Russian Federation
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Omsk Oblast
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Russian Federation
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Moscow
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Russian Federation
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St-Petersburg
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Russian Federation
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Ufa
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Spain
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A Coruña
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Spain
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Andalucia
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Spain
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Madrid
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Spain
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Badalona
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Spain
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Caceres
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Spain
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Castelló
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Spain
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Sabadell
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Spain
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Sevilla
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Spain
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Valencia
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Spain
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Zaragoza
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Taiwan
State/province [81] 0 0
New Taipei City
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Taiwan
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Taipei City
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Cambridgeshire
Country [84] 0 0
United Kingdom
State/province [84] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ImmunoGen, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Gynecologic Oncology Group
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This Phase 3 study is designed to compare the efficacy and safety of mirvetuximab
soravtansine vs. investigator's choice chemotherapy in patients with platinum-resistant
high-grade epithelial ovarian cancer, primary peritoneal, or fallopian tube cancer, whose
tumors express a high-level of FRa. Patients will be, in the opinion of the Investigator,
appropriate for single-agent therapy for their next line of therapy. Folate receptor alpha
(FRa) positivity will be defined by the Ventana FOLR1 (FOLR1-2.1) CDx assay.
Trial website
https://clinicaltrials.gov/show/NCT04209855
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Patrick A Zweidler-McKay, MD, PhD
Address 0 0
ImmunoGen, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Elizabeth Noble
Address 0 0
Country 0 0
Phone 0 0
781-895-0176
Fax 0 0
Email 0 0
Elizabeth.Noble@immunogen.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04209855