A Randomized, Open-Label, Multicenter, Phase 2, Umbrella Study to Evaluate the Preliminary Efficacy, Safety, and Pharmacodynamics of Tislelizumab Monotherapy and Multiple Tislelizumab-based Immunotherapy Combinations With and Without Chemotherapy as Neoadjuvant Treatment in Chinese Patients With Resectable Stage II to IIIA Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 121
- 试验地点
- 14
- 主要终点
- Major Pathological Response (MPR) Rate
研究概览
简要总结
This study was conducted to evaluate the preliminary effectiveness and safety of treatment with tislelizumab alone and in combination with other investigational agents prior to surgery (neoadjuvant treatment) in adults with non-small cell lung cancer (NSCLC) that is able to be removed by surgery.
详细描述
This is a randomized, open-label, multicenter, Phase 2, umbrella study to evaluate the preliminary efficacy, safety, and pharmacodynamics of tislelizumab as monotherapy and in combination with investigational agents as neoadjuvant treatment in Chinese participants with resectable Stage II to IIIA NSCLC. The study is designed with the flexibility of adding treatment arms as new treatments become available or discontinuing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and of modifying the participant population.
The study consisted of a neoadjuvant treatment phase (2 - 4 cycles of treatment), a surgery phase and a follow-up phase.
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
- 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 (ECOG PS) of 0 or 1
- •Histologically confirmed Stage II-IIIA NSCLC (per the Eighth American Joint Committee on Cancer/Union Internationale Contre le Cancer [NSCLC] staging system)
- •Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection with curative intent
- •Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained ≤ 7 days before randomization
- •Provide formalin-fixed paraffin-embedded block (preferred) or at least 15 freshly cut unstained FFPE slides of the primary tumor for biomarker evaluation during screening
排除标准
- •Any prior antineoplastic therapy(ies) for current lung cancer (eg, radiotherapy, targeted therapies, ablation, or other systemic or local antineoplastic treatment)
- •Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-cell immunoglobulin and ITIM domain (TIGIT), anti-lymphocyte activation gene-3 (LAG-3), or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
- •Has mixed small cell lung cancer
- •Participants with large cell neuroendocrine carcinoma (LCNEC)
- •The presence of locally advanced unresectable NSCLC regardless of stage or metastatic disease
- •Known epidermal growth factor receptor (EGFR) sensitizing mutations and/or anaplastic lymphoma kinase (ALK) rearrangement
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Arm 2A: Tislelizumab and Chemotherapy
Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Cisplatin (Drug)
Arm 1A: Tislelizumab Monotherapy
Participants with tumor programmed death protein ligand-1 (PD-L1) expression ≥ 50% received 200 mg tislelizumab intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Tislelizumab (Drug)
Arm 2A: Tislelizumab and Chemotherapy
Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Tislelizumab (Drug)
Arm 2A: Tislelizumab and Chemotherapy
Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Carboplatin (Drug)
Arm 2A: Tislelizumab and Chemotherapy
Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Pemetrexed (Drug)
Arm 2A: Tislelizumab and Chemotherapy
Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Paclitaxel (Drug)
Arm 1B: Tislelizumab + Ociperlimab
Participants with tumor PD-L1 expression ≥ 50% received 200 mg tislelizumab and 900 mg ociperlimab intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Tislelizumab (Drug)
Arm 1B: Tislelizumab + Ociperlimab
Participants with tumor PD-L1 expression ≥ 50% received 200 mg tislelizumab and 900 mg ociperlimab intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Ociperlimab (Drug)
Arm 1C: Alcestobart + Tislelizumab
Participants with tumor PD-L1 expression ≥ 50% received 200 mg tislelizumab and 600 mg alcestobart intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Tislelizumab (Drug)
Arm 1C: Alcestobart + Tislelizumab
Participants with tumor PD-L1 expression ≥ 50% received 200 mg tislelizumab and 600 mg alcestobart intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Alcestobart (Drug)
Arm 2C: Alcestobart + Tislelizumab + Chemotherapy
Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab, 600 mg alcestobart and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Tislelizumab (Drug)
Arm 2C: Alcestobart + Tislelizumab + Chemotherapy
Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab, 600 mg alcestobart and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Alcestobart (Drug)
Arm 2C: Alcestobart + Tislelizumab + Chemotherapy
Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab, 600 mg alcestobart and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Cisplatin (Drug)
Arm 2C: Alcestobart + Tislelizumab + Chemotherapy
Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab, 600 mg alcestobart and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Carboplatin (Drug)
Arm 2C: Alcestobart + Tislelizumab + Chemotherapy
Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab, 600 mg alcestobart and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Pemetrexed (Drug)
Arm 2C: Alcestobart + Tislelizumab + Chemotherapy
Participants with tumor PD-L1 expression < 50% received 200 mg tislelizumab, 600 mg alcestobart and chemotherapy consisting of cisplatin or carboplatin with either pemetrexed or paclitaxel administered intravenously once every 3 weeks for 2-4 cycles followed by surgical removal of the tumor.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Major Pathological Response (MPR) Rate
时间窗: At the time of surgery, approximately Week 16
Tumor tissue and lymph node tissue obtained from surgical resection were sent to a central laboratory according to study pathology manuals for pathological response analysis. MPR rate is defined as the percentage of participants with ≤ 10% residual viable tumor in the resected primary tumor and all resected lymph nodes as assessed by blinded independent pathology review (BIPR). Participants without surgery or pathological results were considered non-responders.
次要结局
- Pathological Complete Response (pCR)(At the time of surgery, approximately Week 16)
- Event-free Survival (EFS)(From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2.)
- Event-free Survival Rate(12 months and 24 months after randomization)
- Overall Survival (OS)(From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2.)
- Overall Survival Rate(12 months and 24 months after randomization)
- Disease-free Survival (DFS)(From randomization until the end of study, maximum time on study was 22 months in Substudy 1 and 13 months in Substudy 2.)
- Disease-free Survival Rate(12 months and 24 months after randomization)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs)(From first dose of study drug until 30 days after last dose or new anticancer treatment, whichever occurred first, or up to 90 days after the last dose for imAEs; maximum duration of treatment was 14 weeks.)
- Feasibility of Surgery(At the time of surgery, approximately Week 16)
- Duration of Surgery(Approximately Week 16)