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

Fallopian Tube Cancer Clinical Trial

— SORAYA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04296890
• Other study ID #: IMGN853-0417
• Secondary ID: 2020-000179-19
• Status: Completed
• Phase: Phase 3
• Start date: July 23, 2020
• Est. completion date: November 16, 2022

Study information

• Verified date: July 2023
• Source: ImmunoGen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 106
• Est. completion date: November 16, 2022
• Est. primary completion date: November 16, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 a (FRa) positivity

6. Patient's tumor must be positive for FRa 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 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 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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Epithelial Ovarian Cancer
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Neoplasms
• Peritoneal Cancer

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Australia	ICON Cancer Care	Auchenflower	Queensland
Australia	Peninsula and South Eastern Haematology & Oncology Group	Frankston	Victoria
Australia	Royal North Shore Hospital	St. Leonards	New South Wales
Australia	St John of God Subiaco Hospital	Subiaco	Western Australia
Belgium	Cliniques Universitaires Saint Luc - lnstitut Roi Albert II	Brussels	Bruxelles
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Belgium	Centre Hopsitalier de l'Ardenne	Libramont	Luxembourg
Belgium	CHU UCL Namur/Site Sainte Elisabeth	Namur
Bulgaria	MHAT "Serdika"	Sofia
Czechia	Všeobecná fakultní nemocnice v Praze	Praha 2	Prague
Germany	KEM	Essen
Germany	UMG Frauenklinik Robert-Koch-Str. 40	Göttingen	Niedersachsen
Germany	Universitätsmedizin Mannheim	Mannheim	Baden-Württemberg
Ireland	Bon Secours Hospital	Cork	Munster
Ireland	Cork University Hospital	Cork	Munster
Ireland	Beaumont Hospital	Dublin
Ireland	Mater Misericordiae University Hospital	Dublin	Leinster
Ireland	St. James's Hospital	Dublin	Leinster
Ireland	University Hospital Waterford	Waterford	Munster
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Ein Kerem Medical center	Jerusalem
Israel	Shaare Zedek 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
Italy	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	Azienda Ospedaliera Ospedale Niguarda Ca'Granda	Milano
Italy	IEO Istituto Europeo di Oncologia	Milano
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
Poland	Specjalistyczna Przychodnia Lekarska Medicus	Chorzów	Silesia
Poland	Instytut Centrum Zdrowia Matki Polki	Lódz	Lódzkie
Poland	Mazurskim Centrum Onkologiiw Olsztynie	Olsztyn	Warminsko-Mazurskie
Spain	Hospital Teresa Herrera - Complejo Hospitalario Universitario A Coruna	A Coruña	Galicia
Spain	Institut Català d'Oncologia Badalona Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Quirón Dexeus	Barcelona
Spain	lnstitut Catala d' Oncologia L' Hospitalet	Barcelona
Spain	Vall d'Hebron Institute of Oncology	Barcelona
Spain	Hospital Reina Sofia de Cordoba	Córdoba
Spain	Institut Català d'Oncología de Girona	Girona
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital Clínico Universitario San Carlos	Madrid
Spain	Hospital La Paz	Madrid	Castellana
Spain	MD Anderson Cancer Centre	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
United States	Northside Hospital	Atlanta	Georgia
United States	Texas Oncology-Austin Central	Austin	Texas
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Women's Cancer Center	Covington	Louisiana
United States	City of Hope Medical Center	Duarte	California
United States	Texas Oncology, P.A. - Fort Worth Cancer Center	Fort Worth	Texas
United States	California Cancer Associates (cCARE)	Fresno	California
United States	Hinsdale Hospital	Hinsdale	Illinois
United States	St. Vincent Gynecologic Oncology	Indianapolis	Indiana
United States	Midwest Oncology Associates/Sarah Cannon	Kansas City	Missouri
United States	Kadlec Clinic Hematology and Oncology	Kennewick	Washington
United States	Rocky Mountain Cancer Centers	Littleton	Colorado
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Texas Oncology, P.A. - McAllen	McAllen	Texas
United States	Froedtert and the Medical College of Wisconsin Department of Obstetrics & Gynecology	Milwaukee	Wisconsin
United States	Sarah Cannon Research Institute / Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai Health System	New York	New York
United States	Stanford School of Medicine	Palo Alto	California
United States	Arizona Oncology Associates	Phoenix	Arizona
United States	Center of Hope at Renown Medical Center	Reno	Nevada
United States	Maryland Oncology Hematology, P.A.	Rockville	Maryland
United States	California Pacific Medical Center Research Institute	San Francisco	California
United States	Sarasota Memorial Health Care System	Sarasota	Florida
United States	Texas Oncology, P.A. - Sugar Land	Sugar Land	Texas
United States	Florida Cancer Specialists Panhandle	Tallahassee	Florida
United States	University of South Florida	Tampa	Florida
United States	Holy Name Medical Center	Teaneck	New Jersey
United States	USOR: Texas Oncology - The Woodlands, Gynecologic Oncology	The Woodlands	Texas
United States	Texas Oncology, P.A. - Tyler	Tyler	Texas
United States	Florida Cancer Specialists Research	West Palm Beach	Florida
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
ImmunoGen, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Overall Survival (OS)	The time from first dose of MIRV until death.	Up to 2 years
Secondary	CA-125 Response	Serum CA-125 response determined using the Gynecologic Cancer Intergroup (GCIG) criteria.	Up to 2 years