A Randomized Phase 2, Open-label Study of Mirvetuximab Soravtansine in Patients With Platinum-resistant Advanced High-grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-alpha Expression Testing 2 Schedules of Administration for Dose Optimization, With a Separate Cohort to Determine Starting Dose in Patients With Moderate Hepatic Impairment
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 110
- 试验地点
- 89
- 主要终点
- Randomized Phase 2 Cohort: Percentage of Participants with Grade >= 2 Treatment-Emergent Corneal Adverse Events (AEs)
研究概览
简要总结
Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess the safety and efficacy of for Mirvetuximab Soravtansine in participants with platinum-resistant advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancer (platinum-resistant ovarian cancer) (PROC) whose tumors express a high level of folate receptor alpha (FRα).
Mirvetuximab Soravtansine (MIRV) is an investigational antibody drug conjugate designed to selectively kill cancer cells. The antibody (protein) part of MIRV targets tumors by delivering a cell-killing drug to cancer cells carrying a protein called folate receptor alpha (FRα). There are 2 cohorts in this study, the Randomized Phase 2 Cohort and the Hepatic Impairment Cohort. In the Randomized Phase 2 Cohort, participants are placed in 1 of 2 groups, called treatment arms. Each treatment arm receives MIRV on a different schedule (on day 1 every 21 days or on days 1 and 15 every 28 days). The Hepatic Impairment Cohort is designed to determine the starting dose of MIRV in patients with moderately abnormal liver function. Around 110 participants will be enrolled in the study at approximately 75 sites worldwide.
The total study duration will be approximately 24 months.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.
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
- •Both Cohorts
- •Participants with a confirmed diagnosis of high-grade serous epithelial ovarian cancer (EOC), primary peritoneal cancer, or fallopian tube cancer.
- •Participants with platinum-resistant disease:
- •Participants with 1 prior line of platinum-based therapy who have received ≥ 4 cycles of platinum and had a response (complete response (CR) or partial response (PR)) followed by radiological progressive disease (PD) between > 3 months and ≤ 6 months after the date of the last dose of platinum.
- •Participants with 2 or 3 prior lines of platinum-based therapy who had radiological PD ≤ 6 months after the date of the last dose of platinum.
- •Participants with progression diagnosed radiographically on or after their most recent line of therapy.
- •Participants with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or
- •Participants with ≥ 1 lesion that meets the definition of measurable disease by RECIST v1.1 (radiologically measured by the investigator).
- •Participants with a tumor that is positive for folate receptor alpha (FRα) expression as determined by the Ventana folate receptor 1 (FOLR1) assay (≥ 75% of tumor staining at 2+ intensity).
排除标准
- •Both Cohorts
- •Participants with endometrioid, clear cell, mucinous, or sarcomatous histology; mixed tumors containing any of the above histologies; or low-grade or borderline ovarian tumor.
- •Participants with primary platinum-refractory disease, defined as disease that did not respond (complete response (CR) or partial response (PR)) or that progressed radiographically within 3 months of the last dose of first-line platinum-containing chemotherapy.
- •Participants with serious concurrent illness or clinically relevant active infection as outlined in the protocol
- •Participants with a history of hemorrhagic or ischemic stroke within 6 months prior to randomization.
研究组 & 干预措施
Hepatic Impairment Cohort : Mirvetuximab Soravtansine
Participants will receive Mirvetuximab Soravtansine on Day 1 of a 21-day cycle. Different doses will be given to groups of patients to identify a safe and effective dose.
干预措施: Mirvetuximab Soravtansine (Drug)
Randomized Phase 2 Cohort: Arm A
Participants will receive Mirvetuximab Soravtansine at the standard dose on Day 1 of a 21-day cycle.
干预措施: Mirvetuximab Soravtansine (Drug)
Randomized Phase 2 Cohort: Arm B
Participants will receive Mirvetuximab Soravtansine at a lower dose than the standard dose on Day 1 and Day 15 of a 28-day cycle .
干预措施: Mirvetuximab Soravtansine (Drug)
结局指标
主要结局
Randomized Phase 2 Cohort: Percentage of Participants with Grade >= 2 Treatment-Emergent Corneal Adverse Events (AEs)
时间窗: Up to Approximately 24 months
An AE is any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered study drug related.
Randomized Phase 2 Cohort: Objective response rate (ORR)
时间窗: Up to Approximately 24 months
ORR is defined as best response of confirmed complete response (CR) or partial response (PR), as assessed by the Investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Hepatic Impairment Cohort: Maximal Concentration (Cmax) of Mirvetuximab Soravtansine
时间窗: Up to Approximately 24 months
Cmax of MIRV
Hepatic Impairment Cohort: Area Under the Plasma Concentration (AUC) of Mirvetuximab Soravtansine
时间窗: Up to Approximately 24 months
AUC of MIRV
Hepatic Impairment Cohort: Trough Concentration (Ctrough) of Mirvetuximab Soravtansine
时间窗: Up to Approximately 24 months
Ctrough of MIRV
Hepatic Impairment Cohort: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine
时间窗: Up to Approximately 24 months
Vss) of MIRV
Hepatic Impairment Cohort: Time to Maximal Concentration (Tmax) of Mirvetuximab Soravtansine
时间窗: Up to Approximately 24 months
Tmax of MIRV
Hepatic Impairment Cohort: Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine
时间窗: Up to Approximately 24 months
t1/2 of MIRV
次要结局
- Randomized Phase 2 Cohort: Percentage of Participants with Treatment-Emergent All-Grade Ocular AEs, Grade >= 2 Peripheral Neuropathy, All-Grade Infusion Reactions, and All-Grade Pneumonitis(Up to Approximately 24 months)
- Randomized Phase 2 Cohort: Progression-Free Survival (PFS)(Up to Approximately 24 months)
- Randomized Phase 2 Cohort: Overall Survival (OS)(Up to Approximately 24 months)
- Randomized Phase 2 Cohort: Percentage of Participants With CA-125 Confirmed Clinical Response Per Gynecologic Cancer Intergroup (GCIG) Criteria(Up to Approximately 24 months)
- Randomized Phase 2 Cohort: Maximal Concentration (Cmax) of Mirvetuximab Soravtansine(Up to Approximately 24 months)
- Randomized Phase 2 Cohort: Area Under the Plasma Concentration (AUC) of Mirvetuximab Soravtansine(Up to Approximately 24 months)
- Randomized Phase 2 Cohort: Trough Concentration (Ctrough) of Mirvetuximab Soravtansine(Up to Approximately 24 months)
- Randomized Phase 2 Cohort: Volume of Distribution at Steady State (Vss) of Mirvetuximab Soravtansine(Up to Approximately 24 months)
- Randomized Phase 2 Cohort: Time to Maximal Observed Concentration (Tmax) of Mirvetuximab Soravtansine(Up to Approximately 24 months)
- Randomized Phase 2 Cohort: Terminal Half-Life (t1/2) of Mirvetuximab Soravtansine(Up to Approximately 24 months)
- Randomized Phase 2 Cohort: Change from baseline in two dosing methods while assessing drug response(Up to Approximately 24 months)
- Both Cohorts: Number of Participants With Treatment-emergent Adverse Events (TEAEs)(Up to Approximately 24 months)
- Both Cohorts: Percentage of Participants with Clinically Significant Vital Sign Measurements as Assessed by the Investigator(Up to Approximately 24 months)
- Both Cohorts: Percentage of Participants with Clinically Significant Laboratory Values (test) as Assessed by the Investigator(Up to Approximately 24 months)
- Both Cohorts: Number of Participants With Clinically Significant Abnormalities in Physical Examination Findings(Up to Approximately 24 months)
- Randomized Phase 2 Cohort: Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1(Up to Approximately 24 months)