A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab Given Concurrently With Platinum-based Chemoradiation Therapy in Patients With Locally Advanced, Unresectable NSCLC (Stage III) (PACIFIC2)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 328
- 试验地点
- 87
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a Phase III, randomized, double-blind, placebo-controlled, multi-center, international study assessing the efficacy and safety of durvalumab given concurrently with platinum-based CRT (durvalumab + standard of care [SoC] CRT) in patients with locally advanced, unresectable NSCLC (Stage III).
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 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Principal inclusion criteria :
- •Subjects with histologically- or cytologically-documented NSCLC
- •Locally advanced, unresectable (Stage III) NSCLC
- •World Health Organisation (WHO) performance status 0-1
- •At least one measurable lesion, not previously irradiated
- •Must have a life expectancy of at least 12 weeks at randomization
排除标准
- •Receipt of prior or current cancer treatment, including but not limited to, radiation therapy, investigational agents, chemotherapy, Durvalumab and mAbs.
- •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.
- •History of allogeneic organ transplantation
- •Active or prior documented autoimmune or inflammatory disorders
- •Uncontrolled intercurrent illness
- •History of another primary malignancy / leptomeningeal carcinomatosis / active primary immunodeficiency
- •Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
- •Mixed small cell and NSCLC histology
- •Any medical contraindication to treatment with platinum-based doublet chemotherapy as listed in the local labelling
- •Known allergy or hypersensitivity to any of the IPs or any of the IP excipients.
- •Patients whose radiation treatment plans are likely to encompass a volume of whole lung receiving ≥20 Gy in total (V20) of more than 35% of lung volume.
研究组 & 干预措施
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
干预措施: Durvalumab (Drug)
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
干预措施: Carboplatin/ Paclitaxel (Drug)
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
干预措施: Cisplatin/ Etoposide (Drug)
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
干预措施: Pemetrexed/ Cisplatin (Drug)
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
干预措施: Pemetrexed/ Carboplatin (Drug)
Arm 1: Durvalumab + platinum-based chemotherapy and radiation
Durvalumab ((MEDI4736) in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive durvalumab as consolidation treatment.
干预措施: Radiation (Radiation)
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
干预措施: Placebo (Other)
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
干预措施: Carboplatin/ Paclitaxel (Drug)
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
干预措施: Cisplatin/ Etoposide (Drug)
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
干预措施: Pemetrexed/ Cisplatin (Drug)
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
干预措施: Radiation (Radiation)
Arm 2: Placebo + platinum-based chemotherapy and radiation
Placebo in concurrence with platinum-based chemo-radiation therapy.
All patients will receive 1 of the following platinum-based standard of care chemotherapy options, based on Investigator discretion, in addition to radiation therapy:
- cisplatin/etoposide
- carboplatin/paclitaxel
- pemetrexed/cisplatin
- pemetrexed/carboplatin
At the completion of standard of care chemoradiation therapy (SoC CRT), patients with complete response, partial response or stable disease will continue to receive placebo as consolidation treatment.
干预措施: Pemetrexed/ Carboplatin (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).
The PFS per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) using blinded independent central review (BICR) assessments was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anti-cancer therapy prior to progression. The PD was defined as at least a 20% increase in the sum of diameters of target lesions. Median PFS was calculated using the Kaplan-Meier technique.
次要结局
- Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab(Pre-dose on Day 1 of Cycles 1, 2 and 4)
- Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at Average Over 12 Months(At screening, 2, 4, 6, 8, 12, 16, and 20 weeks after randomization, then every 8 weeks ±1 week up to 52 weeks, and then every 12 weeks ±1 week thereafter until PFS2. Assessed up to 12 months.)
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From time of signature of informed consent up to 90 days after last dose of study treatment or up to the date of initiation of the first subsequent therapy, whichever occurs first, approximately 1988 days.)
- Objective Response Rate (ORR)(Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).)
- Overall Survival (OS)(From screening until confirmed PD, assessed up to the DCO date (a maximum of approximately 1988 days).)
- Percentage of Participants Alive at 24 Months From Randomization (OS24)(Month 24)
- Complete Response Rate (CRR)(Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).)
- Duration of Response (DoR)(Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).)
- Disease Control Rate (DCR)(Week 24)
- Time to Death or Distant Metastasis (TTDM)(Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).)
- Time From Randomization to Second Progression (PFS2)(Tumour scans performed at screening, 16 weeks ±1 week after randomization, then every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date (a maximum of approximately 1988 days).)
- Serum Concentration of Durvalumab(End of infusion on Week 0, pre-infusion on Weeks 4 and 12, and Month 3 follow-up)