A Randomised, Open-label, Phase III Study of AZD5335 Versus Mirvetuximab Soravtansine in FRα-high and AZD5335 Versus Investigator's Choice Chemotherapy in FRα-low Expressing High-grade Platinum-resistant Epithelial Ovarian Cancer Patients (TREVI-OC-01)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 1,100
- 试验地点
- 299
- 主要终点
- Progression free Survival (PFS)
研究概览
简要总结
The intention of the study is to demonstrate superiority of AZD5335 versus standard of care by assessment of progression-free survival (PFS) in women with high-grade, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, expressing high or low FRα levels.
详细描述
Approximately 1100 adult participants will be enrolled after central FRα testing into two independent cohorts (about 550 FRα-high and 550 FRα-low) and randomized 1:1 within each cohort to receive AZD5335 or the relevant standard of care (mirvetuximab soravtansine in FRα-high; investigator's choice single-agent chemotherapy in FRα-low). Participants will remain on assigned treatment and undergo regular tumor evaluations per RECIST v1.1 until disease progression or another reason for treatment discontinuation.
All participants will be followed for overall survival. An independent data monitoring committee (IDMC) of external experts will periodically review unblinded safety and interim efficacy to confirm participant safety and study integrity.
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
- Single (Outcomes Assessor)
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 with confirmed diagnosis of high-grade serous EOC, primary peritoneal cancer, or fallopian tube cancer.
- •Participants must have platinum-resistant disease:
- •Participants who have only had one prior line of platinum-based therapy must have received at least 4 cycles of platinum, must have had a response (CR or PR) and then progressed between > 3 months and ≤ 6 months after the date of the last dose of platinum.
- •Participants who have received 2 or 3 lines of platinum therapy must have progressed ≤ 6 months after the date of the last dose of platinum.
- •Participants must have radiologically progressed on or after their most recent line of therapy.
- •Participants must have received at least one, but no more than 3, prior systemic lines of anti-cancer therapy, and for whom single-agent therapy is appropriate as the next line of treatment
- •Participants with documented BRCA mutation (germline and/or somatic) must have received prior PARPi if the participant is eligible per approved label and standard-of-care institutional guidelines, except in cases of documented contraindication, precaution or intolerance.
- •Provision of an FFPE tumour tissue sample
排除标准
- •Participants with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumours containing any of the above histologies, or low-grade or borderline ovarian tumour.
- •Primary platinum-refractory disease, defined as disease that did not respond to or has progressed ≤ 3 months after the last dose of first line platinum-containing chemotherapy.
- •Participants with active or chronic corneal disorders, history of corneal transplantation, or active ocular conditions requiring ongoing treatment/monitoring
- •Current signs, symptoms, or clinical investigations consistent with bowel obstruction, including sub-occlusive disease.
- •Participant has non-infectious ILD/pneumonitis or has a history of non-infectious ILD/pneumonitis that required oral or IV steroids or supplemental oxygen, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Prior treatment with any FRα-targeted therapy, including MIRV, or any TOP1i ADC.
- •Major surgical procedure within 4 weeks of the first dose of study intervention
研究组 & 干预措施
AZD5335 in FRa-low cohort
AZD5335 IV (intravenous) in FRa-low cohort
干预措施: AZD5335 (Drug)
AZD5335 in FRa-high cohort
AZD5335 IV (intravenous) in FRa-high cohort
干预措施: AZD5335 (Drug)
Mirvetuximab Soravtansine (MIRV) in FRa-high cohort
MIRV AIBW IV in FRa-high cohort
干预措施: Mirvetuximab Soravtansine (MIRV) (Drug)
Investigator´s choice chemotherapy in FRa-low cohort
Investigator's choice of chemotherapy Paclitaxel IV Pegylated liposomal Doxorubicin (PLD) IV or Topotecan IV in FRa-low cohor
干预措施: Topotecan (Drug)
Investigator´s choice chemotherapy in FRa-low cohort
Investigator's choice of chemotherapy Paclitaxel IV Pegylated liposomal Doxorubicin (PLD) IV or Topotecan IV in FRa-low cohor
干预措施: Pegylated liposomal Doxorubicin (PLD) (Drug)
Investigator´s choice chemotherapy in FRa-low cohort
Investigator's choice of chemotherapy Paclitaxel IV Pegylated liposomal Doxorubicin (PLD) IV or Topotecan IV in FRa-low cohor
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Progression free Survival (PFS)
时间窗: Up to approximately 5 years
PFS is defined as the time from randomization to radiographic progression as assessed by the Investigator per RECIST v1.1, or death due to any cause.
次要结局
- Overall survival (OS)(Up to approximately 5 years)