Tislelizumab Combined With Albumin Paclitaxel + Carboplatin as Neoadjuvant Therapy for Patients With Stage IIIA-IIIB (N2) Lung Squamous Cell Carcinoma: A Single-arm, Single-center, Exploratory Phase II Clinical Study
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Major Pathological Response (MPR)
研究概览
简要总结
Tislelizumab combined with chemotherapy has shown good efficacy and safety in clinical studies of lung adenocarcinoma (RATIONALE 304) and lung squamous cell carcinoma (RATIONALE 307), thus has been approved as the first-line therapy for advanced non-small cell lung cancer (NSCLC) in China. However, there is no data in the field of neoadjuvant therapy for NSCLC. This single-arm, single-center phase II clinical study is designed to evaluate the efficacy, safety and major pathological response (MPR) of Tislelizumab combined with chemotherapy as neoadjuvant therapy in patients with stage IIIA-IIIB (N2) lung squamous cell carcinoma. Biomarkers correlated with efficacy outcomes will also be explored.
详细描述
Tislelizumab combined with chemotherapy has shown good efficacy and safety in clinical studies of lung adenocarcinoma (RATIONALE 304) and lung squamous cell carcinoma (RATIONALE 307), thus has been approved as the first-line therapy for advanced non-small cell lung cancer (NSCLC) in China. However, there is no data in the field of neoadjuvant therapy for NSCLC. This single-arm, single-center phase II clinical study intends to enroll about 30 patients with potentially operable lung squamous cell carcinoma with clinical stages IIIA-IIIB (N2). Participants will intravenously receive tislelizumab (BeiGene, 200mg d1) + albumin paclitaxel 260mg/m2 d1 + carboplatin AUC 5 d1, Q3W, Imaging evaluation is performed after 2 cycles of medication, and the feasibility of surgery is discussed in multiple disciplines. If the evaluation is operable, the lesion will be surgically removed 22-40 days after the last treatment. If it is assessed to be reduced but still inoperable, the original plan will be continued for another cycle. Imaging examinations, tissue NGS (whole-exome sequencing), gene expression profiling (GEP), and PD-L1 expression will be performed at baseline, preoperative and postoperative respectively.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •The age is ≥18 years old and <75 years old.
- •Eastern Cooperative Oncology Group (ECOG) physical status is 0 or
- •Untreated and histologically confirmed squamous cell lung carcinoma.
- •Potentially operable stage IIIA-IIIB (N2) squamous cell lung carcinoma on enrollment (as defined by the American Joint Committee on Cancer 8th Edition).
- •Sufficient pre-treatment tumor tissue samples/peripheral blood samples for biomarker analysis.
- •Sufficient organ functions, including: Haematological status: absolute neutrophil count(ANC) ≥1.5×10^9 /L, platelet count(PLT) ≥100×10^9 /L, hemoglobin(HB) ≥90 g/L; Liver function: alanine glutamate transaminase (ALT) and glutamate transaminase (AST) ≤2.5 x upper limit of normal range (ULN), total bilirubin (TBIL)≤1.5 x upper limit of normal range (ULN); Kidney function: Creatinine(Cr)≤1.5 x upper limit of normal range(ULN) or Creatinine clearance ≥45 ml/min (calculated according to Cockcroft-Gault equation)
排除标准
- •Participants with known EGFR, ALK or ROS1 sensitive mutations.
- •Participants with autoimmune diseases, tuberculosis, active hepatitis or HIV.
- •Participants who are not expected to tolerate surgery, such as patients with cardiopulmonary insufficiency, etc.
- •A history of other malignant tumors in the past 5 years, except for cured cervical carcinoma in situ, cured basal cell carcinoma of the skin and superficial bladder cancer [Ta, Tis & T1].
- •Participants who have used PD-1/PD-L1 and other immunotherapy drugs before.
- •Women of childbearing age as the exclusion criteria.
研究组 & 干预措施
Tislelizumab + Albumin Paclitaxel + Carboplatin
Tislelizumab 200mg d1, Albumin Paclitaxel 260mg/m2 d1, Carboplatin AUC5 d1, Q3W
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Major Pathological Response (MPR)
时间窗: 2-4 weeks after resection
Major Pathological Response (MPR) is evaluated after resection by pathologists, which is defined as a metric of ≤10% residual tumor tissue after neoadjuvant therapy.
Incidence of Treatment-Emergent Adverse Events
时间窗: Through the trial
Adverse events are evaluated by investigators according to CTCAE 5.0.
次要结局
- Overall Response Rate (ORR)(4 weeks after resection)
- Rate of radical resection (R0)(4 weeks after resection)
- Overall survival (OS)(Through the trial)
- Disease-free survival (DFS)(1 year and 2 years after resection)