A Phase III, Double-Blinded, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment With Atezolizumab or Placebo in Combination With Platinum-Based Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 453
- 试验地点
- 119
- 主要终点
- Independent Review Facility (IRF)-Assessed Event Free Survival (EFS)
研究概览
简要总结
This is a randomized, double-blinded study designed to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of neoadjuvant treatment with atezolizumab (MPDL3280A) or placebo in combination with platinum-based chemotherapy in participants with resectable Stage II, IIIA, or select IIIB non-small cell lung cancer (NSCLC) followed by open-label adjuvant/postoperative atezolizumab or best supportive care and monitoring.
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
- Double (Participant, Care Provider)
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 (ECOG) performance status 0 or 1
- •Histologically or cytologically confirmed, resectable Stage II, IIIA, or Select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on the 8th edition of the AJCC/UICC staging system
- •Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection with curative intent
- •Adequate pulmonary and cardiac function to undergo surgical resection
- •Measurable disease as defined by RECIST v1.1
- •Adequate hematologic and end organ function
- •Negative HIV test at screening
- •Negative for active HBV and HCV at screening
- •Adequate tissue for PD-L1 IHC assessment
排除标准
- •NSCLC with histology of large cell neuroendocrine carcinoma or sarcomatoid carcinoma
- •Mixed NSCLC and small cell lung cancer histology
- •Any prior therapy for lung cancer
- •Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated expected curative outcome
- •Non-squamous NSCLC histology with activating ALK and EGFR mutation
- •Pregnant or lactating women
- •History of autoimmune disease
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or evidence of active of active pneumonitis on screening chest Computed Tomography (CT) scan
- •Prior treatment with cluster of differentiation 137 (CD137) agonist or immune checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody
- •Severe infection within 4 weeks prior to randomization
- •Significant history of cardiovascular disease
研究组 & 干预措施
Arm A: Atezolizumab + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
干预措施: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody (Drug)
Arm A: Atezolizumab + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
干预措施: Nab-paclitaxel (Drug)
Arm A: Atezolizumab + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
干预措施: Pemetrexed (Drug)
Arm A: Atezolizumab + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
干预措施: Carboplatin (Drug)
Arm A: Atezolizumab + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
干预措施: Cisplatin (Drug)
Arm A: Atezolizumab + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; atezolizumab + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Post-operative adjuvant treatment will consist of 16-cycles of atezolizumab
干预措施: Gemcitabine (Drug)
Arm B: Placebo + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Participants will receive best supportive care and monitoring after surgery
干预措施: Placebo Comparator (Drug)
Arm B: Placebo + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Participants will receive best supportive care and monitoring after surgery
干预措施: Nab-paclitaxel (Drug)
Arm B: Placebo + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Participants will receive best supportive care and monitoring after surgery
干预措施: Pemetrexed (Drug)
Arm B: Placebo + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Participants will receive best supportive care and monitoring after surgery
干预措施: Carboplatin (Drug)
Arm B: Placebo + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Participants will receive best supportive care and monitoring after surgery
干预措施: Cisplatin (Drug)
Arm B: Placebo + platinum-based chemotherapy
Neoadjuvant treatment will consist of 4 cycles; placebo + platinum-based chemotherapy
Platinum-based chemotherapy may include:
- carboplatin + pemetrexed
- carboplatin + nab-paclitaxel
- cisplatin + pemetrexed
- cisplatin + gemcitabine
Participants will receive best supportive care and monitoring after surgery
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Independent Review Facility (IRF)-Assessed Event Free Survival (EFS)
时间窗: Up to approximately 96 months
IRF-assessed EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, or death from any cause, whichever occurs first.
次要结局
- Objective Response (OR)(Prior to surgery, up to approximately 84 days)
- Length of Surgical Delays(Up to approximately 96 months)
- Investigator-Assessed EFS(Up to approximately 96 months)
- 2-Year and 3-Year OS(Up to approximately 96 months)
- Change from baseline in HRQoL scores(Up to approximately 96 months)
- Percentage of Participants With Adverse Events (AEs)(Up to approximately 96 months)
- Number and Severity of Surgical Related Adverse Events(Up to approximately 96 months)
- Number of Surgical Delays(Up to approximately 96 months)
- Maximum Observed Serum Atezolizumab Concentration (Cmax)(Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 96 months))
- Pathological Complete Response (pCR)(At time of surgery)
- Major Pathological Response (MPR)(At time of surgery)
- Overall Survival (OS)(Up to approximately 96 months)
- Disease-Free Survival (DFS)(Up to approximately 96 months)
- 2-Year and 3-Year Independent Review Facility-Assessed EFS(Up to approximately 96 months)
- 2-Year and 3-Year Investigator-Assessed EFS(Up to approximately 96 months)
- Number of Operative and Post-Operative Complications(Up to approximately 96 months)
- Reasons for Surgical Cancellations(Up to approximately 96 months)
- Minimum Observed Serum Atezolizumab Concentration (Cmin)(Pre-dose on Day 1 of Cycles 1 and 3 (each cylce is 21 days) for Neoadjuvant Treatment; pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 (each cycle is 21 days) for Arm A; at treatment or observation follow-up discontinuation (up to approximately 96 months))
- Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab(Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 96 months))