A Phase III, Double-blind, Placebo-controlled, Randomised, Multicentre, International Study of Durvalumab Plus Oleclumab and Durvalumab Plus Monalizumab in Patients With Locally Advanced (Stage III), Unresectable Non-small Cell Lung Cancer (NSCLC) Who Have Not Progressed Following Definitive, Platinum-Based Concurrent Chemoradiation Therapy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 1,051
- 试验地点
- 202
- 主要终点
- Progression Free Surival (PFS)
研究概览
简要总结
This is a Phase III, randomised, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) or durvalumab (MEDI4736) with monalizumab (IPH2201) in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based cCRT.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-Blind
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
- •Participant must be ≥ 18 years at the time of screening.
- •Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
- •Provision of a tumour tissue sample obtained prior to CRT
- •Documented tumour PD-L1 status by central lab
- •Documented EGFR and ALK wild-type status (local or central).
- •Patients must not have progressed following definitive, platinum based, concurrent chemoradiotherapy
- •Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
- •Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.
- •WHO performance status of 0 or 1 at randomization
- •Adequate organ and marrow function
排除标准
- •History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥5 years before the first dose of study intervention and of low potential risk for recurrence, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours without evidence of disease.
- •Mixed small cell and non-small cell lung cancer histology.
- •Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
- •Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
- •Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy (excluding alopecia).
- •Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy.
- •History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis - regardless of time of onset prior to randomisation. Evidence of active non-CRT induced pneumonitis (≥ Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis - diagnosed in the past 6 months prior to randomization.
- •Active or prior documented autoimmune or inflammatory disorders (with exceptions)
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
研究组 & 干预措施
Arm A: Durvalumab and Oleclumab
Durvalumab on Day 1 of each 28-day cycle + Oleclumab on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months
干预措施: Durvalumab (Drug)
Arm A: Durvalumab and Oleclumab
Durvalumab on Day 1 of each 28-day cycle + Oleclumab on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months
干预措施: Oleclumab (Drug)
Arm B: Durvalumab and Monalizumab
Durvalumab + Monalizumab on Day 1 of each 28-day cycle for up to 12 months. Placebo infusion will be administered on Day 15 of cycles 1 and 2 only
干预措施: Placebo (Other)
Arm B: Durvalumab and Monalizumab
Durvalumab + Monalizumab on Day 1 of each 28-day cycle for up to 12 months. Placebo infusion will be administered on Day 15 of cycles 1 and 2 only
干预措施: Durvalumab (Drug)
Arm B: Durvalumab and Monalizumab
Durvalumab + Monalizumab on Day 1 of each 28-day cycle for up to 12 months. Placebo infusion will be administered on Day 15 of cycles 1 and 2 only
干预措施: Monalizumab (Drug)
Arm C: Durvalumab and Placebo
Durvalumab on Day 1 of each 28-day cycle + Placebo on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months
干预措施: Placebo (Other)
Arm C: Durvalumab and Placebo
Durvalumab on Day 1 of each 28-day cycle + Placebo on Days 1 and 15 of cycles 1 and 2, then on Day 1 of each subsequent 28-day cycle for up to 12 months
干预措施: Durvalumab (Drug)
结局指标
主要结局
Progression Free Surival (PFS)
时间窗: Up to 5 years after first patient randomized.
Progression Free Survival (PFS) as assessed by BICR, per RECIST 1.1.
次要结局
- Progression free survival (PFS) at 6, 12, 18, and 24 months(From date of randomization until 24 months)
- Overall Survival (OS)(Up to 9 years after first patient randomized)
- Objective response rate (ORR)(Up to 5 years after first patient randomized)
- Time from randomization to first date of distant metastasis or death (TTDM)(Up to 5 years after first patient randomized)
- Progression free survival (PFS) as assessed by Investigator(Up to 5 years after first patient randomized)
- Concentration of Durvalumab(From date of randomization until 3 months after date of last IP dose)
- Concentration of Oleclumab(From date of randomization until 3 months after last dose of IP)
- Concentration of Monalizumab(From date of randomization until 3 months after last dose of IP)
- Duration of response (DoR)(Up to 5 years after first patient randomized)
- Time from randomization to second progression (PFS2)(Up to 5 years after first patient randomized)
- Anti-drug antibodies (ADAs)(From date of randomization until 3 months after date of last IP dose)
- Time to deterioration in pulmonary symptoms (TTFCD)(Up to 5 years after last patient randomized)
- Overall survival (OS) at 24 months(Up to 9 years after first patient randomized)
- Time from randomization to start date of first subsequent therapy (TFST)(Up to 9 years after first patient randomized)
- IHC analysis of PD-L1 TC expression(Up to 5 years after first patient randomized)