Chemotherapy Combined with Immune Checkpoint Inhibitors in Patients with ALK-rearranged Non-small Cell Lung Cancer (NSCLC) Who Have Progressed After First-line Alectinib: a Proof-of-concept, Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- PFS
研究概览
简要总结
This study aimed to investigate the combination of chemotherapy and immunotherapy for patients with metastatic ALK fusion-positive non-small cell lung cancer (NSCLC) who had failed from first line Alectinib. Additionally, available biological samples such as blood and tumor tissues were collected to explore potential biomarkers, including but not limited to RNA-seq, whole-exome sequencing (WES), whole-genome sequencing (WGS), immunohistochemistry, and multiplex immunofluorescence.
详细描述
- The investigators collected data from patients with metastatic ALK fusion-positive non-small cell lung cancer (NSCLC) who received first-line Alectinib treatment between April 2017 and July 2021. Our analysis aimed to assess their clinical outcomes and explore the impact of 5' ALK on the treatment response to Alectinib.
- For patients who experienced disease progression after August 2021, they were treated with a combination of chemotherapy and PD-1 monoclonal antibodies with/without Bevacizumab or chemotherapy alone with/without Bevacizumab was observed and recorded data on progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and overall survival (OS) for these patients.
- The investigators collected pre-treatment biological samples for biomarker analysis, including FFPE samples for whole-genome sequencing (WGS), whole-exome sequencing (WES), RNA-seq, and multiplex fluorescence analysis. FFPE samples were also collected for PD-L1 testing. Additionally, pre-treatment blood samples were collected for cytokine analysis, as well as tumor mutational burden (TMB) and T-cell receptor (TCR) testing. The investigators aimed to evaluate the differences in these results between 3' ALK and 5' ALK.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 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
- •≥18，Advanced Non-small Cell Lung Cancer Confirmed by Histopathology
- •ALK -arreaged confirmed by NGS;
- •Received first line treatment Alectinib;
- •Progressed from first-line alectinib;
- •Predicted survival ≥ 12 weeks;
- •Adequate bone marrow hematopoiesis and organ function;
- •Presence of measurable lesions according to RECIST 1.1;
- •Subjects with stable brain metastases may be included in the study.
- •Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
排除标准
- •Patient who do not have the samples for NGS to confirmed ALK status.
- •Subjects who have received any of the following treatments must be excluded:
- •Treatment with molecules such as EGFR, VEGFR antibodies within 4 weeks prior to the first dose of study drug.
- •Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
- •Presence of spinal cord compression or meningeal metastasis.
- •History of other malignant tumors within 2 years.
- •Adverse events (except alopecia of any degree) of CTCAE > grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
- •History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
- •The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
- •Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
- •Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
- •Live vaccine was given 2 weeks before the first medication.
- •Women who are breastfeeding or pregnant.
- •Hypersensitivity to the test drug and the ingredients.
- •Other conditions assessed by the investigator to be unsuitable for participation in the study.
研究组 & 干预措施
Part A: Patients with 3'ALK retained 5'ALK.
Patients with 3'ALK retained 5'ALK who progressed from first line Alectinib were randomized to Arm A: Chemo+ICIs/Chemo+ICIs+BEV and Arm B: Chemo/Chemo+BEV.
干预措施: Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab (Drug)
Part A: Patients with 3'ALK retained 5'ALK.
Patients with 3'ALK retained 5'ALK who progressed from first line Alectinib were randomized to Arm A: Chemo+ICIs/Chemo+ICIs+BEV and Arm B: Chemo/Chemo+BEV.
干预措施: Chemotherapy alone or Chemotherapy with or without Bevacizumab (Drug)
Part B: Patients with 3'ALK.
Patients with 3'ALK who progressed from first line Alectinib were randomized to Arm C: Chemo+ICIs/Chemo+ICIs+BEV and Arm D: Chemo/Chemo+BEV.
干预措施: Chemotherapy alone or Chemotherapy plus Immune Checkpoint Inhibitors with or without Bevacizumab (Drug)
Part B: Patients with 3'ALK.
Patients with 3'ALK who progressed from first line Alectinib were randomized to Arm C: Chemo+ICIs/Chemo+ICIs+BEV and Arm D: Chemo/Chemo+BEV.
干预措施: Chemotherapy alone or Chemotherapy with or without Bevacizumab (Drug)
结局指标
主要结局
PFS
时间窗: From first dose until 28 days after the last dose, up to 24 months
Progression free survival time
次要结局
- OS(Time from first subject dose to study completion, or up to 48 months)
- ORR(From first dose until 28 days after the last dose, up to 24 months)
研究者
Yongchang Zhang
Professor
Hunan Province Tumor Hospital