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

NCT ID: NCT04296890

Last Updated: 2024-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-23
• Study Completion Date: 2022-11-16

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.

Conditions

Epithelial Ovarian Cancer; Peritoneal Cancer; Fallopian Tube Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Mirvetuximab Soravtansine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

IMGN853; MIRV

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

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

ImmunoGen, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Method, MD, MPH, MBA

Role: STUDY_DIRECTOR

ImmunoGen, Inc.

Ursula Matulonis, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Robert Coleman, MD

Role: PRINCIPAL_INVESTIGATOR

The US Oncology Network

Locations

Arizona Oncology Associates

Phoenix, Arizona, United States

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

California Pacific Medical Center Research Institute

San Francisco, California, United States

Rocky Mountain Cancer Centers

Littleton, Colorado, United States

Sarasota Memorial Health Care System

Sarasota, Florida, United States

Florida Cancer Specialists Panhandle

Tallahassee, Florida, United States

University of South Florida

Tampa, Florida, United States

Florida Cancer Specialists Research

West Palm Beach, Florida, United States

Northside Hospital

Atlanta, Georgia, United States

Hinsdale Hospital

Hinsdale, Illinois, United States

St. Vincent Gynecologic Oncology

Indianapolis, Indiana, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Women's Cancer Center

Covington, Louisiana, United States

Maryland Oncology Hematology, P.A.

Rockville, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Midwest Oncology Associates/Sarah Cannon

Kansas City, Missouri, United States

Center of Hope at Renown Medical Center

Reno, Nevada, United States

Holy Name Medical Center

Teaneck, New Jersey, United States

Mount Sinai Health System

New York, New York, United States

Memorial Sloan-Kettering Cancer Center

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. - Fort Worth Cancer Center

Fort Worth, Texas, United States

Texas Oncology, P.A. - McAllen

McAllen, Texas, United States

Texas Oncology, P.A. - Sugar Land

Sugar Land, 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

Froedtert and the Medical College of Wisconsin Department of Obstetrics & Gynecology

Milwaukee, Wisconsin, United States

Royal North Shore Hospital

St Leonards, New South Wales, Australia

ICON Cancer Care

Auchenflower, Queensland, Australia

Peninsula and South Eastern Haematology & Oncology Group

Frankston, Victoria, Australia

St John of God Subiaco Hospital

Subiaco, Western Australia, Australia

Cliniques Universitaires Saint Luc - lnstitut Roi Albert II

Brussels, Brussels Capital, Belgium

Centre Hopsitalier de l'Ardenne

Libramont, Luxembourg, Belgium

UZ Gent

Ghent, , Belgium

UZ Leuven

Leuven, , Belgium

CHU UCL Namur/Site Sainte Elisabeth

Namur, , Belgium

MHAT "Serdika"

Sofia, , Bulgaria

Všeobecná fakultní nemocnice v Praze

Prague, Prague, Czechia

Universitätsmedizin Mannheim

Mannheim, Baden-Wurttemberg, Germany

UMG Frauenklinik Robert-Koch-Str. 40

Göttingen, Lower Saxony, Germany

KEM

Essen, , Germany

Mater Misericordiae University Hospital

Dublin, Leinster, Ireland

St. James's Hospital

Dublin, Leinster, Ireland

Cork University Hospital

Cork, Munster, Ireland

Bon Secours Hospital

Cork, Munster, Ireland

University Hospital Waterford

Waterford, Munster, Ireland

Beaumont Hospital

Dublin, , Ireland

Rambam Medical Center

Haifa, , Israel

Shaare Zedek Medical Center

Jerusalem, , Israel

Hadassah Ein Kerem Medical center

Jerusalem, , Israel

Meir Medical Center

Kfar Saba, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Kaplan Medical Center

Rehovot, , Israel

Ziv Medical Center

Safed, , Israel

Policlinico S. Orsola-Malpighi

Bologna, , Italy

Azienda Socio Santaria Territoriale degli Spedali Civili di Brescia

Brescia, , Italy

Istituto Oncologico Candiolo

Candiolo, , Italy

Ospedale Cannizzaro di Catania

Catania, , Italy

IEO Istituto Europeo di Oncologia

Milan, , Italy

Azienda Ospedaliera Ospedale Niguarda Ca'Granda

Milan, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Napoli, , Italy

Istituto Nazionale Tumori- G. Pascale

Napoli, , Italy

Ospedale S.Maria della Misericordia

Perugia, , Italy

Fondazione Policlinico Universitario A. Gemelli IRCCS

Roma, , Italy

Specjalistyczna Przychodnia Lekarska Medicus

Chorzów, Silesian Voivodeship, Poland

Mazurskim Centrum Onkologiiw Olsztynie

Olsztyn, Warmian-Masurian Voivodeship, Poland

Instytut Centrum Zdrowia Matki Polki

Lodz, Łódź Voivodeship, Poland

Institut Català d'Oncologia Badalona Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital La Paz

Madrid, Castellana, Spain

Hospital Teresa Herrera - Complejo Hospitalario Universitario A Coruna

A Coruña, Galicia, Spain

Hospital Quirón Dexeus

Barcelona, , Spain

Vall d'Hebron Institute of Oncology

Barcelona, , Spain

lnstitut Catala d' Oncologia L' Hospitalet

Barcelona, , Spain

Hospital Reina Sofia de Cordoba

Córdoba, , Spain

Institut Català d'Oncología de Girona

Girona, , Spain

Clinica Universidad de Navarra

Madrid, , Spain

MD Anderson Cancer Centre

Madrid, , Spain

Hospital Clínico Universitario San Carlos

Madrid, , Spain

Hospital Clinico Universitario Virgen de la Arrixaca

Murcia, , Spain

Corporació Sanitaria Parc Taulí

Sabadell, , Spain

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Instituto Valenciano de Oncologia

Valencia, , Spain

Countries

United States; Australia; Belgium; Bulgaria; Czechia; Germany; Ireland; Israel; Italy; Poland; Spain

References

Coleman RL, Lorusso D, Oaknin A, Cecere SC, Denys H, Colombo N, van Gorp T, Konner JA, Romeo Marin M, Harter P, Murphy C, Wang Y, Esteves B, Method M, Matulonis U. Mirvetuximab soravtansine in folate receptor alpha (FRalpha)-high platinum-resistant ovarian cancer: final overall survival and post hoc sequence of therapy subgroup results from the SORAYA trial. Int J Gynecol Cancer. 2024 Aug 5;34(8):1119-1125. doi: 10.1136/ijgc-2024-005401.

Reference Type: DERIVED

PMID: 38858103 (View on PubMed)

Dilawari A, Shah M, Ison G, Gittleman H, Fiero MH, Shah A, Hamed SS, Qiu J, Yu J, Manheng W, Ricks TK, Pragani R, Arudchandran A, Patel P, Zaman S, Roy A, Kalavar S, Ghosh S, Pierce WF, Rahman NA, Tang S, Mixter BD, Kluetz PG, Pazdur R, Amiri-Kordestani L. FDA Approval Summary: Mirvetuximab Soravtansine-Gynx for FRalpha-Positive, Platinum-Resistant Ovarian Cancer. Clin Cancer Res. 2023 Oct 2;29(19):3835-3840. doi: 10.1158/1078-0432.CCR-23-0991.

Reference Type: DERIVED

PMID: 37212825 (View on PubMed)

Matulonis UA, Lorusso D, Oaknin A, Pignata S, Dean A, Denys H, Colombo N, Van Gorp T, Konner JA, Marin MR, Harter P, Murphy CG, Wang J, Noble E, Esteves B, Method M, Coleman RL. Efficacy and Safety of Mirvetuximab Soravtansine in Patients With Platinum-Resistant Ovarian Cancer With High Folate Receptor Alpha Expression: Results From the SORAYA Study. J Clin Oncol. 2023 May 1;41(13):2436-2445. doi: 10.1200/JCO.22.01900. Epub 2023 Jan 30.

Reference Type: DERIVED

PMID: 36716407 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-000179-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IMGN853-0417

Identifier Type: -

Identifier Source: org_study_id