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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Recurrent Ovarian Cancer; Folate Receptor-Alpha Positive
• Intervention / Treatment: Drug: Mirvetuximab Soravtansine; Drug: Lubricating Eye Drops; Drug: Prednisolone acetate ophthalmic suspension 1% eye drops; Drug: Brimonidine tartrate ophthalmic solution eye drops

Detailed 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).

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: ImmunoGen, Inc.; Phone Number: 781-895-0600; Email: 424medical@immunogen.com

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia
      • Monash University - Monash Medical Centre (MMC) - Clayton
• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium
      • Universitair Ziekenhuis Antwerpen (UZA) - Borstkliniek
  • East Flanders
    • Gent, East Flanders, Belgium
      • AZ Sint-Lucas - Campus Sint-Lucas - Borstkliniek
    • Gent, East Flanders, Belgium
      • Universitair Ziekenhuis Gent (UZ Gent)
• Canada
  • Quebec
    • Montreal, Quebec, 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
• France
  • Paris, France
    • Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Cochin
  • Paris, France
    • Groupe Hospitalier Diaconesses Croix Saint-Simon - Hopital de la Croix Saint-Simon
  • Pierre Benite, France
    • Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
• Ireland
  • Dublin, Ireland
    • Bon Secours Hospital - Dublin
  • Dublin, Ireland
    • Mater Misericordiae University Hospital (MMUH) (START Dublin)
• Italy
  • Milan, Italy
    • Istituto Europeo di Oncologia (IEO) (European Institute of Oncology)
• Spain
  • Barcelona, Spain
    • Vall d'Hebron Institut d'Oncologia
  • Barcelona, Spain
    • Parc Taulí
  • Jaen, Spain
    • Complejo Hospitalario de Jaen (University Hospital Ciudad De Jaen)
  • Barcelona
    • Badalona, Barcelona, Spain
      • Institut Catala d'Oncologia (ICO) - Hospital Universitari Germans Trias i Pujol (HUGTP) Location
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Health - University of Colorado Cancer Center (UCCC) - Anschutz Medical Campus (Anschutz Cancer Pavilion) (ACP)
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine - Yale Gynecologic Oncology
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Holy Cross Hospital
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Baystate Regional Cancer Program - D'Amour Center for Cancer Care Location - Gynecologic Oncology
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology
    • Albany, New York, United States, 12208
      • Women's Cancer Care Associates, LLC
    • New York, New York, United States, 10032
      • New York-Presbyterian/Columbia University Medical Center - Herbert Irving Comprehensive Cancer Center (HICCC) - Herbert Irving Pavilion
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute (DCI) - Duke Cancer Center
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center - Harold C. Simmons Comprehensive Cancer Center - University Hospital Gynecologic Oncology Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Participants must have a confirmed diagnosis of epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) with high FRα expression.
• Participant's tumor must be FRα positive (FRα 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 FRα-targeting agents.

Note: Other protocol-defined inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary Prophylactic Steroid Eye Drops; Prednisolone acetate ophthalmic suspension 1% 6 times daily on Days -1 to 4 and 4 times daily (QID) on Days 5 to 8 of each cycle; Lubricating eye drops QID throughout the entire cycle (doses should follow steroid dosing, when given, by approximately 15 minutes); MIRV 6 milligrams (mg)/kilogram (kg) adjusted ideal body weight (AIBW) every 3 weeks (Q3W). Each cycle length = 21 days.	Drug: Mirvetuximab Soravtansine; Mirvetuximab soravtansine is an antibody drug conjugate designed to target folate receptor α (FRα). It consists of the humanized anti-FRα monoclonal antibody (mAb) M9346A attached via a cleavable disulfide linker to the cytotoxic maytansinoid, DM4.; Other Names: IMGN853; MIRV; Drug: Lubricating Eye Drops; Lubricating artificial tears should be administered at least 15 minutes after corticosteroid or brimonidine eye drop administration.; Drug: Prednisolone acetate ophthalmic suspension 1% eye drops; Self-administration of prednisolone acetate ophthalmic suspension 1% eye drops as prescribed by the treating physician.
Experimental: Primary Prophylactic Vasoconstricting Eye Drops; Primary prophylactic brimonidine tartrate ophthalmic solution eye drops 3 times daily (TID) throughout the cycle; Lubricating eye drops QID throughout the entire cycle (doses should follow brimonidine dosing, when given, by approximately 15 minutes); MIRV 6 mg/kg AIBW Q3W. Each cycle length = 21 days.	Drug: Mirvetuximab Soravtansine; Mirvetuximab soravtansine is an antibody drug conjugate designed to target folate receptor α (FRα). It consists of the humanized anti-FRα monoclonal antibody (mAb) M9346A attached via a cleavable disulfide linker to the cytotoxic maytansinoid, DM4.; Other Names: IMGN853; MIRV; Drug: Lubricating Eye Drops; Lubricating artificial tears should be administered at least 15 minutes after corticosteroid or brimonidine eye drop administration.; Drug: Brimonidine tartrate ophthalmic solution eye drops; Self-administration of brimonidine tartrate ophthalmic solution eye drops as prescribed by the treating physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: ImmunoGen, Inc.
• Investigators: Study Director: Sheri Spunt, MD, ImmunoGen, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 30, 2024
• Primary Completion (Estimated): May 26, 2026
• Study Completion (Estimated): May 26, 2027

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Estimated): April 15, 2024

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Eye Diseases; Genital Neoplasms, Female; Wounds and Injuries; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Craniocerebral Trauma; Trauma, Nervous System; Optic Nerve Diseases; Cranial Nerve Diseases; Drug-Related Side Effects and Adverse Reactions; Radiation Injuries; Cranial Nerve Injuries; Optic Nerve Injuries; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Recurrence; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Toxic Optic Neuropathy; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Antineoplastic Agents, Phytogenic; Pharmaceutical Solutions; Immunoconjugates; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Brimonidine Tartrate; Ophthalmic Solutions; Maytansine; Lubricant Eye Drops; Mirvetuximab soravtansine
• Other Study ID Numbers: IMGN853-0424; 2023-505617-24-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No