Clinical trial NCT06365853: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Recurrent Ovarian Cancer
Folate Receptor-Alpha Positive
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2024-04-15
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With MIRV-related Corneal TEAEs (≥ Grade 2) in Asymptomatic Participants
timeFrame: Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
Secondary outcomes:
measure: Number of Participants With Ocular symptom TEAEs in Participants Using Corticosteroid or Vasoconstricting Eye Drop Primary Prophylaxis
timeFrame: Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days
measure: Number of Participants With MIRV-related Corneal TEAEs in Symptomatic Participants
timeFrame: Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
measure: Number of Participants With Ocular exam TEAEs in Asymptomatic Participants and Symptomatic participants
timeFrame: Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
measure: Number of Participants With MIRV-related Corneal TEAEs (≥ Grade 2) in Participants Using Corticosteroid or Vasoconstricting Eye Drop Primary Prophylaxis
timeFrame: Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
measure: Number of Participants with ocular exam TEAEs in Participants using corticosteroid or vasoconstricting eye drop primary prophylaxis
timeFrame: Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
measure: National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) Composite Score
timeFrame: At Cycle 5 Day 1 or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
measure: Area Under the Curve (AUC) of MIRV
timeFrame: 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)
measure: Maximum Serum Concentration (Cmax) of MIRV
timeFrame: 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)
measure: Trough Concentration (Ctrough) of MIRV
timeFrame: 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)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles /ID# 269339
state: California
city: Louisville
country: United States
facility: Norton Healthcare /ID# 269070
state: Kentucky
city: Silver Spring
country: United States
facility: Holy Cross Hospital - Silver Spring /ID# 269344
state: Maryland
city: Saint Louis
country: United States
facility: Mercy David C. Pratt Cancer Center /ID# 269350
state: Missouri
city: Reno
country: United States
facility: The Center Of Hope /ID# 269348
state: Nevada
city: Teaneck
country: United States
facility: Holy Name Medical Center /ID# 269340
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology - Albany Cancer Center /ID# 269345
state: New York
city: Albany
country: United States
facility: Women'S Cancer Care Associates /ID# 269980
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute /ID# 269342
state: North Carolina
city: Akron
country: United States
facility: Summa Health /ID# 269349
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern Medical Center /ID# 269341
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Southeast Hospital /ID# 269347
state: Texas
city: Blacktown
country: Australia
facility: Blacktown Hospital /ID# 269305
state: New South Wales
city: Lambton Heights
country: Australia
facility: Newcastle Private Hosptial /ID# 269306
state: New South Wales
city: Clayton
country: Australia
facility: Monash University Clayton Campus /ID# 269304
state: Victoria
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen /ID# 269310
state: Antwerpen
city: Aalst
country: Belgium
facility: Onze Lieve Vrouw Ziekenhuis Aalst /ID# 269311
state: Oost-Vlaanderen
city: Gent
country: Belgium
facility: AZ Sint-Lucas /ID# 269307
state: Oost-Vlaanderen
city: Gent
country: Belgium
facility: UZ Gent /ID# 269309
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: UZ Leuven /ID# 269308
state: Vlaams-Brabant
city: Liege
country: Belgium
facility: CHU de Liege /ID# 269312
city: Montreal
country: Canada
facility: Universite de Montreal - Hopital Maisonneuve-Rosemont /ID# 268862
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier De L'Universite De Montreal - Hopital Saint-Luc /ID# 269314
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre - Glen Site /ID# 269313
state: Quebec
city: Marseille
country: France
facility: Institut Paoli-Calmettes /ID# 269648
state: Bouches-du-Rhone
city: Tours
country: France
facility: Centre Hospitalier Régional Universitaire de Tours - Hôpital Bretonneau /ID# 269301
state: Indre-et-Loire
city: Paris CEDEX 14
country: France
facility: Hopitaux Universitaires Paris Centre-Hopital Cochin /ID# 269330
state: Paris
city: Pierre Benite
country: France
facility: Hospices Civils de Lyon - Centre Hospitalier Lyon-Sud /ID# 269327
state: Rhone
city: Le Mans
country: France
facility: Clinique Victor Hugo Le Mans /ID# 269985
state: Sarthe
city: Paris
country: France
facility: GH Diaconesses Croix Saint-Simon /ID# 269329
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital /ID# 269334
city: Dublin
country: Ireland
facility: Beaumont Hospital /ID# 268864
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara /ID# 269320
state: Caceres
city: Jaén
country: Spain
facility: Hospital Universitario de Jaén /ID# 269319
state: Jaen
city: Barcelona
country: Spain
facility: Usp Instituto Universitario Dexeus /ID# 269322
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 269315
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal /ID# 269318
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 269321
city: Madrid
country: Spain
facility: Hospital Universitario La Paz /ID# 269302
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe /ID# 269325
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: