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 prespecified 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: Active, not 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 (Actual): 108
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital /ID# 269305
    • Lambton Heights, New South Wales, Australia, 2305
      • Newcastle Private Hosptial /ID# 269306
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health - Monash Medical Centre - Clayton /ID# 269304
• Belgium
  • Liège, Belgium, 4000
    • CHU de Liege /ID# 269312
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Universitair Ziekenhuis Antwerpen /ID# 269310
  • Oost-Vlaanderen
    • Aalst, Oost-Vlaanderen, Belgium, 9300
      • OLV Ziekenhuis Aalst /ID# 269311
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • AZ Sint-Lucas /ID# 269307
    • Ghent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 269309
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Universitair Ziekenhuis Leuven /ID# 269308
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Universite de Montreal - Hopital Maisonneuve-Rosemont /ID# 268862
    • Montreal, Quebec, Canada, H2X 0C1
      • Centre Hospitalier de l'Universite de Montreal /ID# 269314
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre - Glen Site /ID# 269313
• France
  • Paris, France, 75020
    • GH Diaconesses Croix Saint-Simon /ID# 269329
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13273
      • Institut Paoli-Calmettes /ID# 269648
  • Indre-et-Loire
    • Tours, Indre-et-Loire, France, 37000
      • Centre Hospitalier Regional Universitaire de Tours - Hopital Bretonneau /ID# 269301
  • Paris
    • Paris, Paris, France, 75679
      • Hopitaux Universitaires Paris Centre-Hopital Cochin /ID# 269330
  • Rhone
    • Pierre-Bénite, Rhone, France, 69310
      • Hospices Civils de Lyon - Centre Hospitalier Lyon-Sud /ID# 269327
  • Sarthe
    • Le Mans, Sarthe, France, 72000
      • Clinique Victor Hugo Le Mans /ID# 269985
• Ireland
  • Dublin, Ireland, D07 R2WY
    • Mater Misericordiae University Hospital /ID# 269334
  • Dublin, Ireland, D09 XR63
    • Beaumont Hospital /ID# 268864
• Spain
  • Barcelona, Spain, 08028
    • Usp Instituto Universitario Dexeus /ID# 269322
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall de Hebron /ID# 269315
  • Cáceres, Spain, 10003
    • Hospital San Pedro de Alcantara /ID# 269320
  • Jaén, Spain, 23007
    • Hospital Universitario de Jaen /ID# 269319
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal /ID# 269318
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre /ID# 269321
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz /ID# 269302
  • Valencia, Spain, 46026
    • Hospital Universitario y Politecnico La Fe /ID# 269325
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles /ID# 269339
    • San Francisco, California, United States, 94158-2531
      • UCSF Medical Center /ID# 280425
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute - St. Matthews /ID# 269070
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Holy Cross Hospital - Silver Spring /ID# 269344
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Mercy David C. Pratt Cancer Center /ID# 269350
  • Nevada
    • Reno, Nevada, United States, 89511
      • The Center Of Hope /ID# 269348
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center /ID# 269340
  • New York
    • Albany, New York, United States, 12206-5013
      • New York Oncology Hematology - Albany Cancer Center /ID# 269345
    • Albany, New York, United States, 12208
      • Women'S Cancer Care Associates /ID# 269980
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute /ID# 269342
  • Ohio
    • Akron, Ohio, United States, 44304-1407
      • Summa Health /ID# 269349
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas - Southwestern Medical Center /ID# 269341
    • Houston, Texas, United States, 77089
      • Memorial Hermann Southeast Hospital /ID# 269347

Participation Criteria

Eligibility Criteria

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

Description

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 FOLR1 (FOLR-2.1) IUO Assay, or the VENTANA FOLR1 ( FOLR1-2.1) RxDx Assay (hereafter collectively termed VENTANA FOLR1 Assay) (≥ 75% cells exhibit ≥ 2+ 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) before first dose of MIRV;
  2. Focal radiation completed ≥ 2 weeks before 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 before the first dose of MIRV.

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 within ≤ 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 before first dose, presence of papilledema, best corrected visual acuity (BCVA) worse than 20/70 in either eye, 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) on Day 1 of each cycle. 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) on Days 1 to 8 of each cycle (vasoconstricting drops should be started on the day of first infusion and should begin before the first infusion on Cycle 1 Day 1); 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 on Day 1 of each cycle. 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 TEAEs (≥ Grade 2) in Asymptomatic Participants	This endpoint will be assessed in the participants receiving MIRV who are asymptomatic .	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
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)
Number of Participants With Ocular symptom TEAEs in Participants Using Corticosteroid or 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 TEAEs in 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 Ocular exam TEAEs in Asymptomatic Participants and 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 TEAEs (≥ Grade 2) in Participants Using Corticosteroid or 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 ocular exam TEAEs in Participants using corticosteroid or 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)

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Actual): August 21, 2026
• Last Update Submitted That Met QC Criteria: August 20, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Ovarian Neoplasms; Pharmaceutical Solutions; Pharmaceutical Preparations; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Solutions; Specialty Uses of Chemicals; Lubricants; Lubricant Eye Drops; Ophthalmic Solutions; mirvetuximab soravtansine
• Other Study ID Numbers: IMGN853-0424; 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation); 2023-505617-24-00 (Other Identifier: EU CT)

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
• product manufactured in and exported from the U.S.: No