A Phase III, Randomised,Double-Blind,Placebo-Controlled,Study of Durvalumab as Consolidation Therapy in Patients With Locally Advanced,Unresectable NSCLC, Who Have Not Progressed Following Definitive, Platinum-Based Chemoradiation Therapy
概览
- 阶段
- 3 期
- 干预措施
- Placebo
- 疾病 / 适应症
- Carcinoma, Non-Small-Cell Lung
- 发起方
- AstraZeneca
- 入组人数
- 407
- 试验地点
- 87
- 主要终点
- Progression-Free Survival (PFS) (Modified Intent-to-Treat [mITT] Set)
- 状态
- 进行中（未招募）
- 最后更新
- 2个月前
概览
简要总结
This is a Phase III, randomised, double-blind, placebo-controlled, multicentre study assessing the efficacy and safety of durvalumab compared with placebo, as consolidation therapy in patients with locally advanced, unresectable, non-small cell lung cancer (Stage III), who have not progressed following definitive, platinum-based, chemoradiation therapy.
详细描述
Approximately 400 patients will be randomized in a 2:1 to receive treatment with durvalumab or placebo therapy. The primary objective of this study is to assess the efficacy of durvalumab treatment compared with placebo in terms of PFS.
研究者
入排标准
入选标准
- •Age≥18 years
- •Documented NSCLC and present with locally advanced, unresectable (Stage III) disease;
- •Receipt of concurrent or sequential chemoradiation therapy,
- •No progression following definitive, platinum-based, concurrent or sequential chemoradiation therapy
- •World Health Organization (WHO) PS of 0 or 1;
- •No prior exposure to any anti CTLA-4, anti-PD-1, anti-PD-L1, or anti PD L2 antibodies, excluding therapeutic anticancer vaccines
- •Adequate organ and marrow function required
- •Life expectancy of at least 12 weeks
- •Tumor PD-L1 status, with the Ventana SP263 PD-L1 IHC assay determined by a reference laboratory, must be known prior to randomization.
- •Tumour sample requirements are as follows: Provision of a tumour tissue sample (newly acquired sample \<=3 months old is preferred, but an archived sample \<=6 months old is acceptable) in a quantity sufficient to allow for analysis.
排除标准
- •History of allogeneic organ transplantation, or another primary malignancy, or active primary immunodeficiency.
- •Active or prior documented autoimmune or inflammatory disorders
- •Uncontrolled intercurrent illness that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent
- •Active infection including tuberculosis hepatitis B hepatitis C (HCV), or human immunodeficiency virus (positive human immunodeficiency virus \[HIV\] 1/2 antibodies).
- •Mixed small cell and NSCLC histology, sarcomatoid variant
- •Any unresolved toxicity National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 from the prior chemoradiation therapy.
- •Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
- •Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.
研究组 & 干预措施
Placebo Therapy
Placebo (matching placebo for infusion every 4 weeks iv until clinical progression/deterioration or confirmed radiological progression)
干预措施: Placebo
Durvalumab Therapy
Durvalumab (PD-L1 monoclonal antibody)1500 mg every 4 weeks \[q4w\] intravenously \[iv\] until clinical progression/deterioration or confirmed radiological progression)
干预措施: Durvalumab
结局指标
主要结局
Progression-Free Survival (PFS) (Modified Intent-to-Treat [mITT] Set)
时间窗: Tumor scans performed at screening, 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 23-Jun-2024 (a maximum of approximately 2035 days)
The PFS per Response Evaluation Criteria in Solid Tumors 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 disease progression (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 (TLs) and an absolute increase of \>=5 millimeters (mm), taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.
次要结局
- Overall Survival (OS)(Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days))
- Progression-Free Survival (PFS) (Intent-to-Treat [ITT] Set)(Tumor scans performed at screening, 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 23-Jun-2024 (a maximum of approximately 2035 days))
- Percentage of Participants Alive at 24 Months (OS24)(Month 24)
- Objective Response Rate (ORR)(Tumor scans performed at screening, 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 23-Jun-2024 (a maximum of approximately 2035 days))
- Duration of Response (DoR)(Tumor scans performed at screening, 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 23-Jun-2024 (a maximum of approximately 2035 days))
- Percentage of Participants Alive and Progression-Free at 12 and 18 Months (PFS12 and PFS18)(Months 12 and 18)
- Serum Concentration of Durvalumab(End of infusion on Cycle 1 Day 1, pre-infusion on Cycles 2 and 4 Day 1 and Month 3 follow-up (each cycle=28 days))
- Time From Randomization to Second Progression (PFS2)(Tumor scans performed at screening, 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 23-Jun-2024 (a maximum of approximately 2035 days))
- Time to Death or Distant Metastases (TTDM)(Tumor scans performed at screening, 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 23-Jun-2024 (a maximum of approximately 2035 days))
- Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab(Pre-dose on Day 1 of Cycles 1, 2 and 4 (each cycle=28 days))
- Change From Baseline in Patient-Reported Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at Week 132(Baseline (Day 1) and Week 132)
- Number of Participants With Positive Programmed Death Ligand 1 (PD-L1) Status Based on Overall Survival, Progression-Free Survival and Objective Response Rate(Up to 9 years)