A Multicenter, Double-Blind, Randomized Phase 3 Clinical Trial Evaluating the Efficacy and Safety of Sintilimab vs. Placebo, in Combination With Chemotherapy, for First-Line Treatment of Unresectable, Locally Advanced, Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma (ORIENT-15)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 746
- 试验地点
- 47
- 主要终点
- OS in overall population
研究概览
简要总结
This is a randomized, double-blind multi-center, phase III study comparing the efficacy and safety of sintilimab or placebo in combination with chemotherapy as first-line treatment in subjects with unresectable, locally advanced recurrent or metastatic esophageal squamous cell carcinoma.
After the interim analysis conducted by the iDMC, an open-label assignment of experimental arm therapy will continue in regions outside of China, in order to further evaluate the efficacy and safety of sintilimab in combination with chemotherapy in subjects representing the western population with advanced esophageal squamous cell carcinoma
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histopathologically confirmed unresectable, locally advanced, recurrent or metastatic ESCC (excluding mixed adenosquamous carcinoma and other histological subtypes)
- •ECOG PS of 0 or 1
- •Subject must be unsuitable for definitive treatment, such as definitive chemoradiotherapy and/or surgery. For subjects who have received (neo)adjuvant or definitive chemotherapy/radiochemotherapy, time from the completion of last treatment to disease recurrence must be > 6 months Could provide archival or fresh tissues for PD-L1 expression analysis with obtainable results
- •Have at least one measurable lesion as per RECIST v1.1
- •Key exclusion Criteria:
- •ESCC with endoscopy-confirmed near-complete obstruction requiring interventional therapy
- •Post stent implantation in the esophagus or trachea with risk of perforation
- •Received systemic treatment for advanced or metastatic ESCC.
- •Received a cumulative dose of cisplatin ≥ 300 mg/m2 and the last cisplatin dose was within 12 months of randomization or the first dose of study treatment in the open-label phase.
- •High risk of hemorrhage or perforations due to tumor invasion in adjacent organs (aorta or trachea), or have fistula formation.
- •Hepatic metastasis > 50% of the total liver volume.
- •Received palliative therapy for a local lesion within 2 weeks prior to the first dose.
- •Received systemic treatment with Chinese traditional medicines with anti-cancer indications or immunomodulators (including thymosins, interferons, and interleukins) within 2 weeks prior to the first dose of study treatment.
- •Received systemic immunosuppressants within 2 weeks prior to randomization, excluding local use of glucocorticoids administered by nasal, inhaled, or other routes, and systemic glucocorticoids at physiological doses (no more than 10 mg/day of prednisone or equivalents), or glucocorticoids to prevent allergies to contrast media.
排除标准
- 未提供
研究组 & 干预措施
Randomized Part: Experimental: Sintilimab + chemotherapy
Sintilimab in combination with investigator's choice of chemotherapy
TP regimen: Cisplatin + paclitaxel
or
CP regimen: Cisplatin + fluorourcil
干预措施: Sintilimab (Biological)
Randomized Part: Experimental: Sintilimab + chemotherapy
Sintilimab in combination with investigator's choice of chemotherapy
TP regimen: Cisplatin + paclitaxel
or
CP regimen: Cisplatin + fluorourcil
干预措施: Cisplatin (Drug)
Randomized Part: Experimental: Sintilimab + chemotherapy
Sintilimab in combination with investigator's choice of chemotherapy
TP regimen: Cisplatin + paclitaxel
or
CP regimen: Cisplatin + fluorourcil
干预措施: Paclitaxel (Drug)
Randomized Part: Experimental: Sintilimab + chemotherapy
Sintilimab in combination with investigator's choice of chemotherapy
TP regimen: Cisplatin + paclitaxel
or
CP regimen: Cisplatin + fluorourcil
干预措施: Fluorouracil (Drug)
Randomised Part: Active Comparator: Placebo + chemotherapy
Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
干预措施: Cisplatin (Drug)
Randomised Part: Active Comparator: Placebo + chemotherapy
Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
干预措施: Paclitaxel (Drug)
Randomised Part: Active Comparator: Placebo + chemotherapy
Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
干预措施: Fluorouracil (Drug)
Randomised Part: Active Comparator: Placebo + chemotherapy
Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
干预措施: Placebo (Drug)
Open-label part: Sintilimab+ chemotherapy
Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
干预措施: Sintilimab (Biological)
Open-label part: Sintilimab+ chemotherapy
Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
干预措施: Cisplatin (Drug)
Open-label part: Sintilimab+ chemotherapy
Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
干预措施: Paclitaxel (Drug)
Open-label part: Sintilimab+ chemotherapy
Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
干预措施: Fluorouracil (Drug)
结局指标
主要结局
OS in overall population
时间窗: From date of randomization until the date of death from any cause, assessed up to 40 months.
To compare the overall survival of sintilimab vs. placebo, in combination with chemotherapy, for first-line treatment in subjects with unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC)
OS in PD-L1 positive population
时间窗: From date of randomization until the date of death from any cause, assessed up to 40 months.
To compare the OS of sintilimab vs. placebo, in combination with chemotherapy, for first-line treatment in subjects with PD-L1 positive, unresectable, locally advanced, recurrent or metastatic ESCC
次要结局
- ORR in overall population(From date of randomization up to 28 months.)
- PFS in overall populationsubjects in ITT population(From date of randomization up to 28 months)
- DCR in overall population(From date of randomization up to 28 months)
- DoR in overall population(From date of randomization up to 28 months)
- ORR - PD-L1 positive(From date of randomization up to 28 months)
- DCR - PD-L1 positive(From date of randomization up to 28 months)
- DoR - PD-L1 positive(From date of randomization up to 28 months)
- PFS - PD-L1 positive(From date of randomization up to 28 months)