Master Protocol: A Phase 2, Open-label, Multi-arm Study of Tislelizumab in Combination With Investigational Agents With or Without Chemotherapy in Patients With Previously Untreated, Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 400
- 试验地点
- 110
- 主要终点
- Confirmed overall response rate (ORR)
研究概览
简要总结
The purpose of this study is to assess the antitumor activity, safety, and tolerability of tislelizumab plus investigational agent(s) with or without chemotherapy. This study is structured as a master protocol with separate sub- studies. Sub-study 1 includes participants with non-small cell lung cancer (NSCLC) with high programmed cell death protein ligand-1 (PD-L1) expression (≥ 50%), and Sub-study 2 includes participants with NSCLC with low or negative (PD-L1) expression (< 50%).
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
- •Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including nonsquamous or squamous subtypes, that is either locally advanced or recurrent and not eligible for curative surgery and/or definitive chemoradiotherapy, or metastatic NSCLC.
- •No prior systemic therapy administered as the primary treatment for metastatic NSCLC. Prior adjuvant or neoadjuvant chemotherapy, definitive chemoradiation, or adjuvant radiotherapy for locally advanced disease is permitted, provided the last dose of chemotherapy and/or radiotherapy occurred at least 6 months prior to randomization/enrollment.
- •Tumor programmed death-ligand 1 (PD-L1) expression must be evaluable, as determined by a local or central laboratory using archival tumor tissue or a fresh biopsy. Participants with unknown PD-L1 expression are not eligible.
- •At least one measurable lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
排除标准
- •Diagnosis of mixed small cell lung cancer.
- •Known genomic alterations for which effective targeted therapies are available according to local standard of care, including but not limited to:
- •Epidermal growth factor receptor (EGFR) mutations
- •Anaplastic lymphoma kinase (ALK) rearrangements
- •B-Raf proto-oncogene (BRAF) mutations
- •Rearranged during transfection (RET) fusions
- •c-ros oncogene 1 (ROS1) rearrangements
- •Participants with nonsquamous NSCLC and unknown EGFR mutation status must undergo local testing. Those found to have EGFR-sensitizing mutations will be excluded.
- •Prior treatment with immune-based therapies that target immune checkpoint pathways, including:
- •PD-1 (programmed cell death protein 1) inhibitors
- •PD-L1 (programmed death-ligand 1) inhibitors
- •PD-L2 (programmed death-ligand 2) inhibitors
- •TIGIT (T cell immunoreceptor with Ig and ITIM domains) inhibitors
- •LAG-3 (lymphocyte activation gene 3) inhibitors
- •Participants previously treated with these agents in a neoadjuvant, adjuvant, or consolidation setting may be eligible if a treatment-free interval of at least 6 months has elapsed since the last dose and radiologic evidence of recurrence is present.
- •Use of Chinese herbal medicines or Chinese patent medicines intended for cancer control within 14 days prior to randomization/enrollment.
- •Presence of active leptomeningeal disease, untreated or uncontrolled brain metastases, or active autoimmune disease.
- •Note: Additional protocol-defined and sub-study-specific criteria may apply.
研究组 & 干预措施
Sub-study 1: Arm 1A
Tislelizumab + BGB-A445
干预措施: Tislelizumab (Drug)
Sub-study 1: Arm 1A
Tislelizumab + BGB-A445
干预措施: BGB-A445 (Drug)
Sub-study 2: Arm 3B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025
干预措施: Nab paclitaxel (Drug)
Sub-study 2: Arm 3B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025
干预措施: BGB-15025 (Drug)
Sub-study 2: Reference Arm
Tislelizumab + investigator's choice of histology-appropriate chemotherapy
干预措施: Tislelizumab (Drug)
Sub-study 2: Reference Arm
Tislelizumab + investigator's choice of histology-appropriate chemotherapy
干预措施: Carboplatin (Drug)
Sub-study 2: Reference Arm
Tislelizumab + investigator's choice of histology-appropriate chemotherapy
干预措施: Cisplatin (Drug)
Sub-study 2: Reference Arm
Tislelizumab + investigator's choice of histology-appropriate chemotherapy
干预措施: pemetrexed (Drug)
Sub-study 2: Reference Arm
Tislelizumab + investigator's choice of histology-appropriate chemotherapy
干预措施: Paclitaxel (Drug)
Sub-study 2: Arm 2B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007
干预措施: pemetrexed (Drug)
Sub-study 2: Arm 3B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025
干预措施: pemetrexed (Drug)
Sub-study 2: Arm 1B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445
干预措施: pemetrexed (Drug)
Sub-study 2: Arm 1B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445
干预措施: Nab paclitaxel (Drug)
Sub-study 2: Arm 1B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445
干预措施: Paclitaxel (Drug)
Sub-study 2: Reference Arm
Tislelizumab + investigator's choice of histology-appropriate chemotherapy
干预措施: Nab paclitaxel (Drug)
Sub-study 2: Arm 2B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007
干预措施: Paclitaxel (Drug)
Sub-study 2: Arm 2B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007
干预措施: LBL-007 (Drug)
Sub-study 2: Arm 2B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007
干预措施: Cisplatin (Drug)
Sub-study 2: Arm 2B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007
干预措施: Carboplatin (Drug)
Sub-study 2: Arm 2B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007
干预措施: Nab paclitaxel (Drug)
Sub-study 2: Arm 3B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025
干预措施: Carboplatin (Drug)
Sub-study 2: Arm 3B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025
干预措施: Cisplatin (Drug)
Sub-study 2: Arm 2B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + LBL-007
干预措施: Tislelizumab (Drug)
Sub-study 2: Arm 3B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025
干预措施: Tislelizumab (Drug)
Sub-study 2: Arm 3B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-15025
干预措施: Paclitaxel (Drug)
Sub-study 1: Arm 2A
Tislelizumab + LBL-007
干预措施: Tislelizumab (Drug)
Sub-study 1: Arm 2A
Tislelizumab + LBL-007
干预措施: LBL-007 (Drug)
Sub-study 1: Arm 3A
Tislelizumab + BGB-15025
干预措施: Tislelizumab (Drug)
Sub-study 1: Reference Arm Tislelizumab alone
Tislelizumab alone
干预措施: Tislelizumab (Drug)
Sub-study 1: Arm 3A
Tislelizumab + BGB-15025
干预措施: BGB-15025 (Drug)
Sub-study 2: Arm 1B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445
干预措施: BGB-A445 (Drug)
Sub-study 2: Arm 1B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445
干预措施: Tislelizumab (Drug)
Sub-study 2: Arm 1B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445
干预措施: Carboplatin (Drug)
Sub-study 2: Arm 1B
Tislelizumab + investigator's choice of histology-appropriate chemotherapy + BGB-A445
干预措施: Cisplatin (Drug)
结局指标
主要结局
Confirmed overall response rate (ORR)
时间窗: Up to 6 months
ORR is defined as the percentage of participants with partial or complete response, as assessed by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1
次要结局
- Progression-free survival (PFS)(Up to 1 year)
- Duration of Response (DOR)(Up to 1 year)
- Clinical Benefit Rate (CBR)(Up to 6 months)
- Disease Control Rate (DCR)(Up to 6 months)
- Number of participants with adverse events (AEs)(From the first dose of study drug(s) to 90 days after initiation of new anticancer therapy, death, withdrawal of consent, or loss to follow-up, whichever occurs first, up to approximately 2 years)