A Phase 2, Multicenter, Open-label, 2-Cohort Study to Investigate the Efficacy and Safety of PET Guided Neoadjuvant Treatment With Tislelizumab (BGB-A317) Plus Chemotherapy/Chemoradiotherapy in Patients With Resectable Esophageal Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 70
- 试验地点
- 8
- 主要终点
- Pathological Complete Response (pCR) Rate
研究概览
简要总结
The purpose of this study is to evaluate the pathological complete response (pCR) in participants receiving tislelizumab plus chemotherapy/chemoradiotherapy as neoadjuvant treatment.
详细描述
This study enrolled participants with esophageal squamous cell carcinoma who were eligible to have their tumor removed by surgery (also called surgical resection). The treatment phase of the study included the following:
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Induction therapy, in which participants received 1 cycle of chemotherapy;
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Neoadjuvant therapy (neoadjuvant refers to treatment that occurs before surgery, which can make the tumor easier to remove). In this study participants received neoadjuvant therapy based on their response to induction therapy. Response to induction therapy was assessed using the maximum standardized uptake value (SUVmax) measured using a Positron Emission Tomography (PET) scan. The SUV number refers to the level of brightness on the PET scan which reflects metabolic activity; increased metabolic activity can indicate cancerous growth.
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Participants with a decrease in SUVmax of 35% or more after induction therapy received neoadjuvant treatment with tislelizumab plus chemotherapy.
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Participants with a decrease in SUVmax less than 35% after induction therapy received neoadjuvant treatment with tislelizumab plus chemotherapy and radiotherapy.
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Surgery to remove the remaining tumor (resection) was to occur 4-6 weeks after completion of neoadjuvant treatment.
After surgery participants were followed until death, lost to follow-up, withdrawal of consent, or until the study was completed
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group Performance Status of 0 or
- •Histologically confirmed esophageal squamous cell carcinoma (ESCC).
- •Stage cT1-2N+M0 and cT3NanyM0 (per The American Joint Committee on Cancer 8th Edition).
- •Evaluation by the investigator to confirm eligibility for an R0 resection with curative intent.
- •Adequate hematologic and organ function, defined by protocol-specified laboratory test results obtained within 14 days before first dose.
排除标准
- •Ineligible for treatment with any of the chemotherapy doublets of protocol-specified chemotherapy.
- •Any prior therapy for current ESCC, including investigational agents, chemotherapy, radiotherapy, targeted therapy agents, or prior therapy with an anti-programmed cell death protein-1, anti-programmed cell death protein ligand-1, anti-programmed cell death protein ligand-2, or any other antibody or drug specifically targeting T-Cell co-stimulation or checkpoint pathways.
- •History of fistula due to primary tumor invasion.
- •Participants with high risk of fistula or sign of perforation evaluated by investigator.
- •Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days before first dose.
- •* Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent) and topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption, and short course (≤ 7 days) of corticosteroid prescribed prophylactically or for the treatment of a non-autoimmune condition are permitted.
- •Active autoimmune diseases or history of autoimmune diseases that may relapse.
- •* Controlled Type I diabetes, hypothyroidism only requiring hormone replacement, controlled celiac disease, skin diseases (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- •History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases.
- •With infections requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis infection.
- •Severe infections within 4 weeks before first dose, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
- •Receive therapeutic oral or intravenous antibiotics within 2 weeks before first dose.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort A (Responder)
Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in positron emission tomography (PET) Standardized Uptake Value (SUV)max ≥ 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and chemotherapy doublet (cisplatin + paclitaxel) for 2 cycles. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.
干预措施: Tislelizumab (Drug)
Cohort A (Responder)
Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in positron emission tomography (PET) Standardized Uptake Value (SUV)max ≥ 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and chemotherapy doublet (cisplatin + paclitaxel) for 2 cycles. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.
干预措施: Paclitaxel (Drug)
Cohort A (Responder)
Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in positron emission tomography (PET) Standardized Uptake Value (SUV)max ≥ 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and chemotherapy doublet (cisplatin + paclitaxel) for 2 cycles. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.
干预措施: Cisplatin (Drug)
Cohort A (Responder)
Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in positron emission tomography (PET) Standardized Uptake Value (SUV)max ≥ 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and chemotherapy doublet (cisplatin + paclitaxel) for 2 cycles. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.
干预措施: Surgical resection (Procedure)
Cohort B (Non-responder)
Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in PET SUVmax < 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and investigator-chosen chemotherapy doublet (paclitaxel + cisplatin or 5-fluorouracil + cisplatin) for 2 cycles plus concurrent radiotherapy. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.
干预措施: Tislelizumab (Drug)
Cohort B (Non-responder)
Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in PET SUVmax < 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and investigator-chosen chemotherapy doublet (paclitaxel + cisplatin or 5-fluorouracil + cisplatin) for 2 cycles plus concurrent radiotherapy. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.
干预措施: Paclitaxel (Drug)
Cohort B (Non-responder)
Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in PET SUVmax < 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and investigator-chosen chemotherapy doublet (paclitaxel + cisplatin or 5-fluorouracil + cisplatin) for 2 cycles plus concurrent radiotherapy. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.
干预措施: Cisplatin (Drug)
Cohort B (Non-responder)
Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in PET SUVmax < 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and investigator-chosen chemotherapy doublet (paclitaxel + cisplatin or 5-fluorouracil + cisplatin) for 2 cycles plus concurrent radiotherapy. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.
干预措施: 5-fluorouracil (Drug)
Cohort B (Non-responder)
Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in PET SUVmax < 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and investigator-chosen chemotherapy doublet (paclitaxel + cisplatin or 5-fluorouracil + cisplatin) for 2 cycles plus concurrent radiotherapy. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.
干预措施: Radiotherapy (Radiation)
Cohort B (Non-responder)
Participants received induction therapy of one 21-day cycle with cisplatin and paclitaxel administered on Day 1. Following the induction phase, participants with a decrease in PET SUVmax < 35% then received neoadjuvant therapy consisting of 200 mg tislelizumab on Day 1 of each 21-day cycle for 3 cycles and investigator-chosen chemotherapy doublet (paclitaxel + cisplatin or 5-fluorouracil + cisplatin) for 2 cycles plus concurrent radiotherapy. After neoadjuvant treatment, participants were assessed for disease resectability and underwent surgical resection of the tumor approximately 4 to 6 weeks later.
干预措施: Surgical resection (Procedure)
结局指标
主要结局
Pathological Complete Response (pCR) Rate
时间窗: pCR was determined from samples taken during surgery; surgery occurred 4-6 weeks after the last dose of chemotherapy, approximately Day 71-86
The pCR rate was defined as the percentage of participants with absence of residual tumor in the resected primary tumor and all resected lymph nodes after completion of neoadjuvant treatment. pCR rates were assessed by a pathologist at each site.
次要结局
- R0 Resection Rate(Resection was planned to occur 4-6 weeks after the last dose of chemotherapy, approximately Day 71-86)
- 1-year/3-year Disease-free Survival (DFS) Rate(1 year and 3 years after surgery)
- 1-year/3-year Event-free Survival (EFS) Rate(1 year and 3 years after first dose date)
- Objective Response Rate (ORR)(ORR was assessed prior to surgery, Day 71 to 86)
- Number Of Participants Experiencing Treatment-Emergent Adverse Events(From the first dose of study drug up to 30 days after last dose of any component of treatment or surgery or the initiation of subsequent anticancer therapy, whichever occurred first. Up to approximately 9 months.)