A Study of Ocular Toxicity Evaluation and Mitigation During Treatment With Mirvetuximab Soravtansine in Participants With Recurrent Ovarian Cancer With High Folate Receptor-Alpha Expression

Recurrent Ovarian Cancer Clinical Trial

Official title:

A Randomized Phase 2 Study of Ocular Toxicity Evaluation and Mitigation During Treatment With Mirvetuximab Soravtansine in Patients With Recurrent Ovarian Cancer With High Folate Receptor-Alpha Expression

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06365853
• Other study ID #: IMGN853-0424
• Secondary ID: 2023-505617-24-0
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 30, 2024
• Est. completion date: May 26, 2027

Study information

• Verified date: April 2024
• Source: ImmunoGen, Inc.
• Contact: ImmunoGen, Inc.
• Phone: 781-895-0600
• Email: 424medical[@]immunogen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the incidence rate and severity of pre-specified mirvetuximab soravtansine (MIRV)-related ocular treatment-emergent adverse events (TEAEs) and assess prophylaxis strategies in all participants (symptomatic and asymptomatic) undergoing prospective ophthalmic evaluation with recurrent ovarian cancer (participants with either platinum-sensitive ovarian cancer [PSOC] or platinum-resistant ovarian cancer [PROC]) with high folate receptor alpha (FRα) expression.

Description:

Participants will be randomized (1:1) to 1 of 2 ocular adverse event (AE) risk mitigation strategy arms (primary prophylactic steroid eye drops versus primary prophylactic vasoconstricting eye drops).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: May 26, 2027
• Est. primary completion date: May 26, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Participants must have a confirmed diagnosis of epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) with high FRa expression.
• Participant's tumor must be FRa positive (FRa high) as defined by either the Ventana folate receptor 1 (FOLR1) (FOLR1-2.1) CDX Assay or Ventana FOLR1 (FOLR1-2.1) RxDx Assay (hereafter collectively termed: Ventana FOLR1 Assay) (=75% cells exhibit 2 or 3+ membrane-staining intensity).
• Participants with known breast cancer susceptibility gene (BRCA) mutations (tumor or germline) must have received poly (ADP-ribose) polymerase inhibitors (PARPi).
• Participants must have completed prior therapy within the specified times below:

1. Systemic antineoplastic therapy = 5 half-lives or 4 weeks (whichever is shorter) prior to first dose of MIRV;

2. Focal radiation completed = 2 weeks prior to the first dose of MIRV.

• Participants must have stabilized or recovered (Grade 1 or baseline) from all prior therapy-related toxicities (except alopecia).
• Women of childbearing potential (WOCBP) must agree to use highly effective contraceptive method(s) while on MIRV and for = 7 months after the last dose; and must have a negative pregnancy test = 4 days prior to the first dose of MIRV.

Key Exclusion Criteria:

• Participants with borderline ovarian tumor or non-epithelial histology or mixed histology including borderline or non-epithelial histology will be excluded.
• PROC participants with primary platinum-refractory disease, defined as disease that did not respond to (complete response [CR] or partial response [PR]) or progressed = 3 months of the last dose of first line platinum-containing chemotherapy.
• Participants with > Grade 1 peripheral neuropathy per National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0).
• Participants with significant active or chronic corneal disorders (for example, corneal dystrophies, degenerations, limbal stem cell deficiency), history of corneal transplantation, significant ocular inflammatory conditions (for example, active or recurrent uveitis), or other active ocular conditions requiring ongoing treatment/monitoring, such as uncontrolled glaucoma, active diabetic retinopathy with macular edema, macular degeneration requiring treatment = 90 days prior to first dose, presence of papilledema, best corrected visual acuity (BCVA) worse than 20/70, or monocular vision.
• Participants receiving corticosteroid or vasoconstricting eyedrops at baseline or within 5 weeks of Cycle 1 Day 1.
• Participants who received prior treatment with MIRV or other FRa-targeting agents. Note: Other protocol-defined inclusion and exclusion criteria may apply.

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Neoplasms
• Recurrence
• Recurrent Ovarian 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 monoclonal antibody (mAb) M9346A attached via a cleavable disulfide linker to the cytotoxic maytansinoid, DM4.
• Lubricating Eye Drops
Lubricating artificial tears should be administered at least 15 minutes after corticosteroid or brimonidine eye drop administration.
• Prednisolone acetate ophthalmic suspension 1% eye drops
Self-administration of prednisolone acetate ophthalmic suspension 1% eye drops as prescribed by the treating physician.
• Brimonidine tartrate ophthalmic solution eye drops
Self-administration of brimonidine tartrate ophthalmic solution eye drops as prescribed by the treating physician.

Locations

Country	Name	City	State
Australia	Monash University - Monash Medical Centre (MMC) - Clayton	Clayton	Victoria
Belgium	Universitair Ziekenhuis Antwerpen (UZA) - Borstkliniek	Edegem	Antwerp
Belgium	AZ Sint-Lucas - Campus Sint-Lucas - Borstkliniek	Gent	East Flanders
Belgium	Universitair Ziekenhuis Gent (UZ Gent)	Gent	East Flanders
Canada	McGill University Health Centre (MUHC) - The Montreal General Hospital (MGH) - Cedars Cancer Centre	Montreal	Quebec
Canada	Universite de Montreal - Centre Hospitalier de l'Universite de Montreal (CHUM) - Hopital Notre-Dame	Montreal	Quebec
France	Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Cochin	Paris
France	Groupe Hospitalier Diaconesses Croix Saint-Simon - Hopital de la Croix Saint-Simon	Paris
France	Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud	Pierre Benite
Ireland	Bon Secours Hospital - Dublin	Dublin
Ireland	Mater Misericordiae University Hospital (MMUH) (START Dublin)	Dublin
Italy	Istituto Europeo di Oncologia (IEO) (European Institute of Oncology)	Milan
Spain	Institut Catala d'Oncologia (ICO) - Hospital Universitari Germans Trias i Pujol (HUGTP) Location	Badalona	Barcelona
Spain	Parc Taulí	Barcelona
Spain	Vall d'Hebron Institut d'Oncologia	Barcelona
Spain	Complejo Hospitalario de Jaen (University Hospital Ciudad De Jaen)	Jaen
United States	New York Oncology Hematology	Albany	New York
United States	Women's Cancer Care Associates, LLC	Albany	New York
United States	University of Colorado Health - University of Colorado Cancer Center (UCCC) - Anschutz Medical Campus (Anschutz Cancer Pavilion) (ACP)	Aurora	Colorado
United States	University of Texas Southwestern Medical Center - Harold C. Simmons Comprehensive Cancer Center - University Hospital Gynecologic Oncology Clinic	Dallas	Texas
United States	Duke Cancer Institute (DCI) - Duke Cancer Center	Durham	North Carolina
United States	Yale School of Medicine - Yale Gynecologic Oncology	New Haven	Connecticut
United States	New York-Presbyterian/Columbia University Medical Center - Herbert Irving Comprehensive Cancer Center (HICCC) - Herbert Irving Pavilion	New York	New York
United States	Holy Cross Hospital	Silver Spring	Maryland
United States	Baystate Regional Cancer Program - D'Amour Center for Cancer Care Location - Gynecologic Oncology	Springfield	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
ImmunoGen, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Ireland,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With MIRV-related Corneal AEs (= Grade 2) in Asymptomatic Participants	This endpoint will be assessed in the participants receiving MIRV who are asymptomatic (defined as ocular symptom assessment = Grade 1), in the 3-week period prior to the examination.	Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
Secondary	Number of Participants With All Ocular TEAEs in Participants Using Corticosteroid Versus Vasoconstricting Eye Drop Primary Prophylaxis		Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
Secondary	Number of Participants With MIRV-related Corneal AEs and All Ocular TEAEs in Asymptomatic Versus Symptomatic Participants		Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
Secondary	Number of Participants With MIRV-related Corneal AEs and All Ocular TEAEs in Participants Using Corticosteroid Versus Vasoconstricting Eye Drop Primary Prophylaxis		Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
Secondary	National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) Composite Score		At Cycle 5 Day 1 or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
Secondary	Area Under the Curve (AUC) of MIRV		Day 1 and Day 8 of Cycles 1 through 4 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
Secondary	Maximum Serum Concentration (Cmax) of MIRV		Day 1 and Day 8 of Cycles 1 through 4 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
Secondary	Trough Concentration (Ctrough) of MIRV		Day 1 and Day 8 of Cycles 1 through 4 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)