SORAYA: 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

Sponsor

ImmunoGen, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04296890

Collaborator

(none)

106

Enrollment

Locations

Arm

28.3

Anticipated Duration (Months)

1.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Epithelial Ovarian Cancer Peritoneal Cancer Fallopian Tube Cancer	Drug: Mirvetuximab Soravtansine	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

106 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

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)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)

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 23, 2020

Actual Primary Completion Date :

Nov 16, 2021

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Duration of Response (DOR) [Up to 2 years]
The time from initial Investigator-assessed response (CR or PR) until progressive disease (PD) as assessed by the Investigator
Adverse Events (AEs) [Up to 2 years]
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).
Progression-Free Survival (PFS) [Up to 2 years]
The time from first dose of MIRV until Investigator-assessed radiological progressive disease (PD) or death, whichever occurs first.
Overall Survival (OS) [Up to 2 years]
The time from first dose of MIRV until death.
CA-125 Response [Up to 2 years]
Serum CA-125 response determined using the Gynecologic Cancer Intergroup (GCIG) criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Patients must have progressed radiographically on or after their most recent line of anticancer therapy.
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
Patient's tumor must be positive for FRα expression as defined by the Ventana FOLR1 Assay
Patients must have at least 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the Investigator)
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:
Adjuvant ± neoadjuvant considered 1 line of therapy
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)
Therapy changed due to toxicity in the absence of progression will be considered part of the same line (i.e., not counted independently)
Hormonal therapy will be counted as a separate line of therapy unless it was given as maintenance
Patients must have an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
Patients must have completed prior therapy within the specified times below:
Systemic antineoplastic therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to first dose of MIRV
Focal radiation completed at least 2 weeks prior to first dose of MIRV
Patients must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia)
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
Patients must have adequate hematologic, liver and kidney functions defined as:
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
Platelet count ≥ 100 x 10^9/L (100,000/μL) without platelet transfusion in the prior 10 days
Hemoglobin ≥ 9.0 g/dL without packed red blood cell (PRBC) transfusion in the prior 21 days
Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN
Serum bilirubin ≤ 1.5 x ULN (patients with documented diagnosis of Gilbert syndrome are eligible if total bilirubin < 3.0 x ULN)
Serum albumin ≥ 2 g/dL
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
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
WCBP must have a negative pregnancy test within the 4 days prior to the first dose of MIRV

Exclusion Criteria:

Male patients
Patients with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, or low-grade/borderline ovarian tumor
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
Patients with prior wide-field radiotherapy (RT) affecting at least 20 percent of the bone marrow
Patients with > Grade 1 peripheral neuropathy per Common Terminology Criteria for Adverse Events (CTCAE)
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
Patients with serious concurrent illness or clinically relevant active infection, including, but not limited to the following:
Active hepatitis B or C infection (whether or not on active antiviral therapy)
Human immunodeficiency virus (HIV) infection
Active cytomegalovirus infection
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

Patients with a history of multiple sclerosis (MS) or other demyelinating disease and/or Lambert-Eaton syndrome (paraneoplastic syndrome)
Patients with clinically significant cardiac disease including, but not limited to, any of the following:
Myocardial infarction ≤ 6 months prior to first dose
Unstable angina pectoris
Uncontrolled congestive heart failure (New York Heart Association > class II)
Uncontrolled ≥ Grade 3 hypertension (per CTCAE)
Uncontrolled cardiac arrhythmias
Patients with a history of hemorrhagic or ischemic stroke within 6 months prior to enrollment
Patients with a history of cirrhotic liver disease (Child-Pugh Class B or C)
Patients with a previous clinical diagnosis of noninfectious interstitial lung disease (ILD), including noninfectious pneumonitis
Patients requiring use of folate-containing supplements (eg, folate deficiency)
Patients with prior hypersensitivity to monoclonal antibodies (mAb)
Women who are pregnant or breastfeeding
Patients who received prior treatment with MIRV or other FRα-targeting agents
Patients with untreated or symptomatic central nervous system (CNS) metastases
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

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

Contacts and Locations

Locations

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