REFRaME-O1: A Phase 2/3 Open-label Study Evaluating the Efficacy and Safety of Luveltamab Tazevibulin (STRO-002) Versus Investigator's Choice (IC) Chemotherapy in Women With Relapsed Platinum-resistant Epithelial Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers) Expressing Folate Receptor Alpha (FOLR1)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 600
- 试验地点
- 63
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
A Phase 2/3 study to investigate the efficacy and safety of luveltamab tazevibulin versus IC chemotherapy in women with ovarian cancer (including fallopian tube or primary peritoneal cancers) expressing FOLR1.
详细描述
This is a randomized, multicenter, international, open-label, 2-part, Phase 2/3 study designed to assess the efficacy and safety of luveltamab tazevibulin versus IC chemotherapy in subjects with relapsed platinum-resistant epithelial ovarian cancer expressing FOLR1.
Part 1 will consist of 2 luveltamab tazevibulin dosing cohorts (Cohort A and Cohort B), with subjects randomized 1:1. Part 1 will be used to select the optimized dosing regimen.
Part 2 will further evaluate the efficacy and safety of the selected dosing regimen versus IC chemotherapy.
Luveltamab tazevibulin will be administered intravenously (IV) over a 1-hour infusion time every 3 weeks.
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
- •High grade serous epithelial ovarian cancer, fallopian tube or primary peritoneal cancer
- •Age ≥ 18 years
- •ECOG performance status 0 to 1
- •Positive FOLR1 expression per central laboratory testing
- •Relapsed platinum-resistant epithelial ovarian cancer and received a total of 1 to 3 prior regimens
- •Prior bevacizumab treatment is required, if labeled and available as standard of care per institutional guidelines, unless subject has documented contraindication
- •At least 1 measurable target lesion per RECIST v1.1
- •Adequate organ function
排除标准
- •Low grade (Grade 1) ovarian carcinoma, clear cell, mucinous, endometrioid, sarcomatous, and mixed histology ovarian carcinomas
- •Prior treatment with a FOLR1- targeting ADCs or with ADCs that contain a tubulin inhibitor
- •Primary platinum-refractory disease
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or to antibody-related fusion protein treatment
- •Pre-existing clinically significant ocular disorders, severe chronic obstructive pulmonary disease or asthma, clinically significant cardiac or cerebrovascular disease, or other significant concurrent, uncontrolled medical condition
- •Previous solid organ transplantation
- •History or clinical signs of meningeal or active central nervous system involvement
- •Concurrent participation in another therapeutic treatment trial
研究组 & 干预措施
Luveltamab tazevibulin dose Cohort A
5.2 mg/kg q3w with prophylactic pegfilgrastim for 2 cycles followed by 4.3 mg/kg q3w for Cycle 3 onwards
干预措施: Luveltamab tazevibulin (Drug)
Luveltamab tazevibulin dose Cohort A
5.2 mg/kg q3w with prophylactic pegfilgrastim for 2 cycles followed by 4.3 mg/kg q3w for Cycle 3 onwards
干预措施: Pegfilgrastim (Drug)
Luveltamab tazevibulin dose Cohort B
4.3 mg/kg q3w
干预措施: Luveltamab tazevibulin (Drug)
Part 2: IC Chemotherapy
- Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 q4w or 1000mg/m2 on Days 1 and 8 q3w
- Paclitaxel 80 mg/m2 on Days 1, 8, and 15 q4w
- Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 q4w
- Topotecan 4.0 mg/m2on Day 1, 8, and 15 q4w or 1.25 mg/m2 on Days 1 - 5 q3w
干预措施: Gemcitabine (Drug)
Part 2: IC Chemotherapy
- Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 q4w or 1000mg/m2 on Days 1 and 8 q3w
- Paclitaxel 80 mg/m2 on Days 1, 8, and 15 q4w
- Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 q4w
- Topotecan 4.0 mg/m2on Day 1, 8, and 15 q4w or 1.25 mg/m2 on Days 1 - 5 q3w
干预措施: Paclitaxel (Drug)
Part 2: IC Chemotherapy
- Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 q4w or 1000mg/m2 on Days 1 and 8 q3w
- Paclitaxel 80 mg/m2 on Days 1, 8, and 15 q4w
- Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 q4w
- Topotecan 4.0 mg/m2on Day 1, 8, and 15 q4w or 1.25 mg/m2 on Days 1 - 5 q3w
干预措施: Pegylated liposomal doxorubicin (Drug)
Part 2: IC Chemotherapy
- Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 q4w or 1000mg/m2 on Days 1 and 8 q3w
- Paclitaxel 80 mg/m2 on Days 1, 8, and 15 q4w
- Pegylated Liposomal Doxorubicin (PLD) 40 mg/m2 q4w
- Topotecan 4.0 mg/m2on Day 1, 8, and 15 q4w or 1.25 mg/m2 on Days 1 - 5 q3w
干预措施: Topotecan (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: up to 24 months
Best response of complete response (CR) or partial response (PR) per RECIST 1.1.
Progression Free Survival (PFS)
时间窗: up to 24 months
time between the date of first dose and the first date of documented progression or death
次要结局
- Incidence and severity of adverse events [Safety and tolerability](up to 24 months)
- Quality of life (QLQ-OV28)(up to 24 months)
- Overall Survival (OS)(up to 24 months)
- Duration of Response (DOR)(up to 24 months)