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
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 108
- 试验地点
- 80
- 主要终点
- Number of Participants With MIRV-related Corneal TEAEs (≥ Grade 2) in Asymptomatic Participants
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •Participants who received prior treatment with MIRV or other FRα-targeting agents. Note: Other protocol-defined inclusion and exclusion criteria may apply.
研究组 & 干预措施
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.
干预措施: Lubricating Eye Drops (Drug)
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.
干预措施: Prednisolone acetate ophthalmic suspension 1% eye drops (Drug)
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.
干预措施: Brimonidine tartrate ophthalmic solution eye drops (Drug)
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.
干预措施: Lubricating Eye Drops (Drug)
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.
干预措施: Mirvetuximab Soravtansine (Drug)
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.
干预措施: Mirvetuximab Soravtansine (Drug)
结局指标
主要结局
Number of Participants With MIRV-related Corneal TEAEs (≥ Grade 2) in Asymptomatic Participants
时间窗: Cycle 1 Day 1 up to 18 weeks or at the 30-day follow-up visit, whichever is earlier (cycle length = 21 days)
This endpoint will be assessed in the participants receiving MIRV who are asymptomatic .
次要结局
- 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))
- 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))