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

Официальное название

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

Обзор

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.

Подробное описание

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).

Вмешательства

• Препарат 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.
• Препарат Lubricating Eye Drops
  Lubricating artificial tears should be administered at least 15 minutes after corticosteroid or brimonidine eye drop administration.
• Препарат Prednisolone acetate ophthalmic suspension 1% eye drops
  Self-administration of prednisolone acetate ophthalmic suspension 1% eye drops as prescribed by the treating physician.
• Препарат Brimonidine tartrate ophthalmic solution eye drops
  Self-administration of brimonidine tartrate ophthalmic solution eye drops as prescribed by the treating physician.

Первичные конечные точки

• Number of Participants With MIRV-related Corneal TEAEs (≥ Grade 2) in Asymptomatic Participants [Срок оценки: Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)]

Вторичные конечные точки (9)

• Number of Participants With Ocular symptom TEAEs in Participants Using Corticosteroid or Vasoconstricting Eye Drop Primary Prophylaxis [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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)]

Критерии участия

Критерии включения

• 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:

• Systemic antineoplastic therapy ≥ 5 half-lives or 4 weeks (whichever is shorter) before first dose of MIRV;
• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 12 центров

• University of California Los Angeles /ID# 269339 — Los Angeles
• Norton Cancer Institute - St. Matthews /ID# 269070 — Louisville
• Holy Cross Hospital - Silver Spring /ID# 269344 — Silver Spring
• Mercy David C. Pratt Cancer Center /ID# 269350 — St Louis
• The Center Of Hope /ID# 269348 — Reno
• Holy Name Medical Center /ID# 269340 — Teaneck
• New York Oncology Hematology - Albany Cancer Center /ID# 269345 — Albany
• Women'S Cancer Care Associates /ID# 269980 — Albany
• … и ещё 4 центра

Испания · 8 центров

• Hospital San Pedro de Alcántara /ID# 269320 — Cáceres
• Hospital Universitario de Jaén /ID# 269319 — Jaén
• Usp Instituto Universitario Dexeus /ID# 269322 — Barcelona
• Hospital Universitario Vall de Hebron /ID# 269315 — Barcelona
• Hospital Universitario Ramon y Cajal /ID# 269318 — Madrid
• Hospital Universitario 12 de Octubre /ID# 269321 — Madrid
• Hospital Universitario La Paz /ID# 269302 — Madrid
• Hospital Universitario y Politecnico La Fe /ID# 269325 — Valencia

Бельгия · 6 центров

• Universitair Ziekenhuis Antwerpen /ID# 269310 — Edegem
• OLV Ziekenhuis Aalst /ID# 269311 — Aalst
• AZ Sint-Lucas /ID# 269307 — Ghent
• UZ Gent /ID# 269309 — Ghent
• Universitair Ziekenhuis Leuven /ID# 269308 — Leuven
• CHU de Liege /ID# 269312 — Liège

Франция · 6 центров

• Institut Paoli-Calmettes /ID# 269648 — Marseille
• Centre Hospitalier Régional Universitaire de Tours - Hôpital Bretonneau /ID# 269301 — Tours
• Hopitaux Universitaires Paris Centre-Hopital Cochin /ID# 269330 — Paris
• Hospices Civils de Lyon - Centre Hospitalier Lyon-Sud /ID# 269327 — Pierre-Bénite
• Clinique Victor Hugo Le Mans /ID# 269985 — Le Mans
• GH Diaconesses Croix Saint-Simon /ID# 269329 — Paris

Австралия · 3 центра

• Blacktown Hospital /ID# 269305 — Blacktown
• Newcastle Private Hosptial /ID# 269306 — Lambton Heights
• Monash Health - Monash Medical Centre - Clayton /ID# 269304 — Clayton

Канада · 3 центра

• Universite de Montreal - Hopital Maisonneuve-Rosemont /ID# 268862 — Montreal
• Hospital Notre-Dame Du Centre Hospitalier De L'Universite De Montreal /ID# 269314 — Montreal
• McGill University Health Centre - Glen Site. /ID# 269313 — Montreal

Ирландия · 2 центра

• Mater Misericordiae University Hospital /ID# 269334 — Dublin
• Beaumont Hospital /ID# 268864 — Dublin

Идентификаторы

NCT: NCT06365853 · IMGN853-0424 · 2023-505617-24-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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