A Phase II, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Patients With Previously Untreated Locally Advanced Resectable Stage II, IIIA, or Select IIIB Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 21
- 主要终点
- Number of Participants With Surgical Delays
研究概览
简要总结
This study will evaluate the surgical safety and feasibility of atezolizumab plus tiragolumab alone or in combination with platinum-based chemotherapy as neoadjuvant treatment for participants with previously untreated locally advanced non-small cell lung cancer (NSCLC). The study will also evaluate the efficacy, pharmacokinetics, immunogenicity, and safety of atezolizumab plus tiragolumab alone or in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by adjuvant atezolizumab plus tiragolumab or adjuvant platinum-based chemotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 Stage II, IIIA, or select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology
- •Eligible for R0 resection with curative intent at the time of screening
- •Adequate pulmonary function to be eligible for surgical resection with curative intent
- •Eligible to receive a platinum-based chemotherapy regimen
- •Measurable disease, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- •Availability of a representative tumor specimen that is suitable for determination of PD-L1 status
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Normal life expectancy, excluding lung cancer mortality risk
- •Adequate hematologic and end-organ function
- •Negative human immunodeficiency virus (HIV) test at screening
- •Negative serology for active hepatitis B virus (HBV) and active hepatitis C virus (HCV) at screening
排除标准
- •NSCLC with histology of large cell neuroendocrine carcinoma, sarcomatoid carcinoma, or NSCLC not otherwise specified
- •Small cell lung cancer (SCLC) histology or NSCLC with any component of SCLC
- •Any prior therapy for lung cancer
- •Active or history of autoimmune disease or immune deficiency
- •History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
- •Active tuberculosis
- •Significant cardiovascular disease
- •NSCLC with an activating EGFR mutation or ALK fusion oncogene
- •Known c-ros oncogene 1 (ROS1) rearrangement
- •History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with negligible risk of metastasis or death
- •Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety
- •Prior treatment with CD127 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, anti-TIGIT, and anti-PD-L1 therapeutic antibodies
- •Treatment with systemic immunostimulatory agents
- •Treatment with systemic immunosuppressive medication
- •Pregnancy or breastfeeding
研究组 & 干预措施
Cohort A (PD-L1 High)
Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Atezolizumab (Drug)
Cohort A (PD-L1 High)
Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Tiragolumab (Drug)
Cohort A (PD-L1 High)
Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Carboplatin (Drug)
Cohort A (PD-L1 High)
Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Cisplatin (Drug)
Cohort B (PD-L1 All Comers)
All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Atezolizumab (Drug)
Cohort A (PD-L1 High)
Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Pemetrexed (Drug)
Cohort A (PD-L1 High)
Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Gemcitabine (Drug)
Cohort A (PD-L1 High)
Participants with high programmed death-ligand 1 (PD-L1) expression level will be enrolled in Cohort A and receive neoadjuvant atezolizumab plus tiragolumab for 4 cycles, followed by surgical resection and either adjuvant atezolizumab plus tiragolumab for 16 cycles or adjuvant chemotherapy for 4 cycles at the discretion of the investigator.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Paclitaxel (Drug)
Cohort B (PD-L1 All Comers)
All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Tiragolumab (Drug)
Cohort B (PD-L1 All Comers)
All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Carboplatin (Drug)
Cohort B (PD-L1 All Comers)
All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Cisplatin (Drug)
Cohort B (PD-L1 All Comers)
All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Pemetrexed (Drug)
Cohort B (PD-L1 All Comers)
All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Gemcitabine (Drug)
Cohort B (PD-L1 All Comers)
All comers, which are participants with any PD-L1 expression level, will be enrolled in Cohort B and receive neoadjuvant atezolizumab plus tiragolumab plus chemotherapy for 4 cycles, followed by surgical resection and adjuvant atezolizumab plus tiragolumab for 16 cycles.
Chemotherapy may include:
- cisplatin/carboplatin + pemetrexed (for non-squamous only)
- carboplatin + gemcitabine (for squamous only)
- carboplatin + paclitaxel
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Number of Participants With Surgical Delays
时间窗: Up to approximately 4.7 months
Participants were scheduled to undergo surgical resection of their tumor upon completion of four cycles of neo-adjuvant therapy. Prior to the surgery, the attending surgeon and medical oncologist assessed the participant to check if it was clinically feasible for them to undergo surgery (pre-surgical assessment). Surgery was to be done within 30 days of the pre-surgical assessment visit. Assessment of surgical delays were made by assessing the data entered in the electronic case report forms (eCRFs).
Number of Participants With Operative and Post-operative Complications
时间窗: From day of surgery up to end of safety follow-up (up to approximately 17.5 months)
Participants who underwent surgical resection of their tumor and had intraoperative or post-operative complications were reported.
Number of Participants With Surgical Cancellations Related to Study Treatment
时间窗: Up to approximately 4.7 months
Participants were scheduled to undergo surgical resection of their tumor upon completion of four cycles of neo-adjuvant therapy. Prior to the surgery, the attending surgeon and medical oncologist assessed the participant for to check if it was clinically feasible for them to undergo surgery (pre-surgical assessment). Surgery was to be done within 30 days of the pre-surgical assessment visit. Assessment of surgical delays were made by assessing the data entered in the eCRFs.
Number of Participants With Adverse Events (AEs)
时间窗: From signing of informed consent to up to 90 days after the final dose of study treatment (Up to approximately 1.7 years)
AE=any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any of the following: Any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product; Any new disease or exacerbation of an existing disease; Recurrence of an intermittent medical condition not present at baseline; Any deterioration in a laboratory value or other clinical test that is associated with symptoms or leads to a change in study treatment or concomitant treatment or discontinuation from study treatment; AEs that are related to a protocol-mandated intervention, including those that occur prior to assignment of study treatment.
Major Pathological Response (MPR) Rate
时间窗: At the time of surgical resection (From Day 114 to Day 144)
MPR rate was defined as the percentage of participants who achieved MPR. MPR was defined as ≤10% residual viable tumor at the time of surgical resection in the primary tumor, as assessed by the local pathology laboratory. Patients who did not proceed to surgery were considered as non-responders for MPR. 95% confidence interval (CI) was calculated using the Wilson Score Method. Percentages have been rounded off.
次要结局
- Serum Concentrations of Tiragolumab at Specified Timepoints(Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12, 16; 30 minutes (min) post-infusion Cycle 1 Day 1; (Cycle=21 days))
- Percentage of Participants With Pathological Complete Response (pCR)(At the time of surgical resection (From Day 114 to Day 144))
- Event-free Survival (EFS)(Up to approximately 3.8 years)
- Serum Concentrations of Atezolizumab at Specified Timepoints(Prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, 8, 12, and 16; 30 minutes (min) post-infusion Day 1 of Cycle 1; (Cycle=21 days))
- Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab(Up to approximately 3.8 years)
- Percentage of Participants With ADAs to Tiragolumab(Up to approximately 3.8 years)