A Phase III, Double-blind, Placebo-controlled, Multi-center International Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III Non-small Cell Lung Cancer (AEGEAN)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 825
- 试验地点
- 1
- 主要终点
- Pathological Complete Response (pCR) in modified intent-to-treat (mITT) population
研究概览
简要总结
This is a Phase III, randomized, double-blind, placebo-controlled, multi-center international study assessing the activity of durvalumab and chemotherapy administered prior to surgery compared with placebo and chemotherapy administered prior to surgery in terms of pathological complete response.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Newly diagnosed and previously untreated patients with histologically or cytologically documented NSCLC with resectable (Stage IIA to select [ie, N2] Stage IIIB) disease
- •World Health Organization (WHO)/ECOG PS of 0 or 1 at enrollment
- •At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline
- •No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines
- •Adequate organ and marrow function
- •Confirmation of a patient's tumour PD-L1 status
- •Provision of sufficient tumour biopsy sample for evaluation and confirmation of EGFR and ALK status
- •Planned surgery must comprise lobectomy, sleeve resection, or bilobectomy
排除标准
- •History of allogeneic organ transplantation
- •Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome)
- •History of another primary malignancy
- •History of active primary immunodeficiency
- •Active infection including tuberculosis hepatitis B and C, or human immunodeficiency virus
- •Deemed unresectable NSCLC by multidisciplinary evaluation
- •Patients who have pre-operative radiotherapy treatment as part of their care plan
- •Patients who have brain metastases or spinal cord compression
- •Stage IIIB N3 and Stages IIIC, IVA, and IVB NSCLC
- •Known allergy or hypersensitivity to any of the study drugs or excipients
- •Existence of more than one primary tumour such as mixed small cell and NSCLC histology
- •Patients whose planned surgery at enrollment includes any of the following procedures: pneumonectomy, segmentectomies, or wedge resections
- •Patients with a documented test result confirming the presence of EGFRm or ALK translocation
研究组 & 干预措施
Arm 1: Durvalumab with platinum-based chemotherapy
Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Durvalumab (Drug)
Arm 1: Durvalumab with platinum-based chemotherapy
Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Carboplatin (Drug)
Arm 1: Durvalumab with platinum-based chemotherapy
Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Cisplatin (Drug)
Arm 1: Durvalumab with platinum-based chemotherapy
Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Pemetrexed (Drug)
Arm 1: Durvalumab with platinum-based chemotherapy
Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Paclitaxel (Drug)
Arm 1: Durvalumab with platinum-based chemotherapy
Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Gemcitabine (Drug)
Arm 1: Durvalumab with platinum-based chemotherapy
Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Surgery (Procedure)
Arm 2: Placebo with platinum-based chemotherapy
Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Placebo (Other)
Arm 2: Placebo with platinum-based chemotherapy
Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Carboplatin (Drug)
Arm 2: Placebo with platinum-based chemotherapy
Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Cisplatin (Drug)
Arm 2: Placebo with platinum-based chemotherapy
Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Pemetrexed (Drug)
Arm 2: Placebo with platinum-based chemotherapy
Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Gemcitabine (Drug)
Arm 2: Placebo with platinum-based chemotherapy
Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Paclitaxel (Drug)
Arm 2: Placebo with platinum-based chemotherapy
Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity
The platinum-based chemotherapy will be based on tumour histology and Investigator discretion:
- cisplatin with pemetrexed
- carboplatin with pemetrexed
- carboplatin with paclitaxel
- cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
干预措施: Surgery (Procedure)
结局指标
主要结局
Pathological Complete Response (pCR) in modified intent-to-treat (mITT) population
时间窗: Up to approximately 15 weeks after randomization
Defined as the lack of any viable tumour cells after complete evaluation in the resected lung cancer specimen and all sampled regional lymph nodes.
Event-Free Survival (EFS) in modified intent to treat (mITT) population
时间窗: Up to 5.5 years after first patient randomized.
An event is defined as documented RECIST 1.1 local or distant recurrence of lung cancer; death due to any cause; disease progression that precludes surgery or discovered upon attempting surgery that prevents completion of surgery.
次要结局
- To assess disease-related symptoms and HRQoL (EORTC QLQ-LC13) in patients treated with durvalumab + chemotherapy prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy prior to surgery followed by placebo post-surgery(From date of screening to 6 months after last dose of IP)
- Event-free survival (EFS) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population(From date of randomization to 5.5 years after randomization)
- To assess disease-related symptoms and HRQoL (EORTC QLQ-C30) in patients treated with durvalumab + chemotherapy prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy prior to surgery followed by placebo post-surgery(From date of screening to 6 months after last dose of IP)
- Disease-free survival (DFS) in modified resected population(From date of randomization to approximately 5.5 years after date of resection)
- Disease-Free Survival (DFS) in PD-L1-TC ≥1% patients in modified resected population(From date of randomization to 5.5 years after date of resection)
- To assess the PK of durvalumab in blood(From date of randomization to 2 months after resection)
- Major Pathological Response (mPR) in modified intent to treat (mITT) population(Up to approximately 15 weeks after randomization)
- Overall Survival (OS) in modified intent to treat (mITT) population(From date of randomization to 5.5 years after randomization)
- pCR in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population(Up to approximately 15 weeks after randomization)
- Major Pathological Response (mPR) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population(Up to approximately 15 weeks after randomization)
- Overall Survival (OS) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population(From date of randomization to 5.5 years after randomization.)
- Presence of ADA for durvalumab(From date of randomization to 3 months after last dose of IP)