Induced and Concurrent Serplulimab Plus Chemoradiotherapy Followed by Toripalimab Maintenance Therapy for Stage III-IVA Cervical Cancer: a Prospective, Multicenter, Randomized, Open Controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Progression-Free Survival(PFS) at Month 36
研究概览
简要总结
This study is a prospective, multicenter, randomized, open controlled clinical trial aimed at evaluating the effectiveness and safety of serplulimab plus chemoradiotherapy in FIGO 2018 stage III or IVA cervical squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma patients who have not received prior treatment.
详细描述
Cervical cancer is the most prevalent malignant tumor of the female reproductive system in China, with an estimated 150,700 new cases and 55,700 new deaths annually. Concurrent chemoradiotherapy (CRT) remains the standard treatment for locally advanced cervical cancer (LACC). However, for high-risk LACC (HR-LACC) patients, the 2-year progression-free survival (PFS) rate is only 57%-62%, and the 5-year overall survival (OS) rate is 52%-64%, which are the leading causes of patient mortality. The KEYNOTE-A18 study demonstrated that the combination of pembrolizumab and CRT reduced the progression risk and death risk by 30% and 27%, respectively, for HR-LACC patients. Following this, the FDA approved pembrolizumab in combination with CRT for the treatment of newly diagnosed stages III-IVA cervical cancer in January 2024. This prospective, multicenter, randomized, controlled clinical trial study aims to evaluate the effectiveness and safety of serplulimab induced and combined chemoradiotherapy in FIGO 2018 stage III or IVA cervical squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma patients who have not received prior treatment.
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 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years and ≤ 75 years at time of study entry.
- •Has histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix.
- •The International Federation of Gynecology and Obstetrics (FIGO) 2018 Stages III-IVA.
- •Diagnosed with PD-L1-positive (combined positive score ≥1).
- •Has not previously received any definitive surgical, radiation, or systemic therapy for cervical cancer.
- •WHO/ECOG performance status of 0 or
- •Patient must have at least one measurable disease as defined by RECIST 1.
排除标准
- •Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent o..
- •Ongoing participation in another clinical study, or planned initiation of treatment in this study less than 28 days from the end of treatment in the previous clinical study.
- •Known history of serious allergy to any active ingredie or any excipients list in monoclonal antibody.
- •The patient has other factors that, in the judgment of the investigator, may lead to forced early termination of the study.
研究组 & 干预措施
Serplulimab + chemoradiotherapy , Serplulimab maintenance
Participants receive serplulimab 300 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 3 cycles followed by serplulimab 300 mg IV on Day 1 of each 6-week cycle (Q3W) for an additional 15 cycles. During the Q3W dosing period of serplulimab, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV or carboplatin (AUC=2) once per week (QW) for 5 or 6 weeks plus external beam radiotherapy followed by brachytherapy not to exceed 8 weeks.
干预措施: Serplulimab (Drug)
Serplulimab + chemoradiotherapy , Serplulimab maintenance
Participants receive serplulimab 300 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 3 cycles followed by serplulimab 300 mg IV on Day 1 of each 6-week cycle (Q3W) for an additional 15 cycles. During the Q3W dosing period of serplulimab, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV or carboplatin (AUC=2) once per week (QW) for 5 or 6 weeks plus external beam radiotherapy followed by brachytherapy not to exceed 8 weeks.
干预措施: Cisplatin (Drug)
Serplulimab + chemoradiotherapy , Serplulimab maintenance
Participants receive serplulimab 300 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 3 cycles followed by serplulimab 300 mg IV on Day 1 of each 6-week cycle (Q3W) for an additional 15 cycles. During the Q3W dosing period of serplulimab, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV or carboplatin (AUC=2) once per week (QW) for 5 or 6 weeks plus external beam radiotherapy followed by brachytherapy not to exceed 8 weeks.
干预措施: Carboplatin (Drug)
Serplulimab + chemoradiotherapy , Serplulimab maintenance
Participants receive serplulimab 300 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 3 cycles followed by serplulimab 300 mg IV on Day 1 of each 6-week cycle (Q3W) for an additional 15 cycles. During the Q3W dosing period of serplulimab, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV or carboplatin (AUC=2) once per week (QW) for 5 or 6 weeks plus external beam radiotherapy followed by brachytherapy not to exceed 8 weeks.
干预措施: Brachytherapy and External Beam Radiotherapy (Radiation)
Concurrent chemoradiotherapy
Participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV or carboplatin (AUC=2) once per week (QW) for 5 or 6 weeks plus external beam radiotherapy followed by brachytherapy not to exceed 8 weeks.
干预措施: Cisplatin (Drug)
Concurrent chemoradiotherapy
Participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV or carboplatin (AUC=2) once per week (QW) for 5 or 6 weeks plus external beam radiotherapy followed by brachytherapy not to exceed 8 weeks.
干预措施: Carboplatin (Drug)
Concurrent chemoradiotherapy
Participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV or carboplatin (AUC=2) once per week (QW) for 5 or 6 weeks plus external beam radiotherapy followed by brachytherapy not to exceed 8 weeks.
干预措施: Brachytherapy and External Beam Radiotherapy (Radiation)
结局指标
主要结局
Progression-Free Survival(PFS) at Month 36
时间窗: Up to approximately 46 months.
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, or by histopathologic confirmation of suspected disease progression, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Unequivocal progression of non-target lesions is also considered PD. PFS data will be cumulated to a certain cut-off date and the analysis will be performed via Kaplan-Meier approach to estimate the PFS rate at Month 36 using the entire PFS data up to the cut-off date.
次要结局
- Overall Survival (OS) at Month 36(Up to approximately 46 months)
- Objective Response Rate (ORR)(Baseline up to approximately 36 months)
- Complete Response Rate（CRR）(Baseline up to approximately 36 months)
- Time to the first disease progression （TTP）(Up to approximately 24 months)
- Duration of response (DOR)(Up to approximately 24 months)
研究者
LING YING WU
Professor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences