A Phase III, Open-label, Randomised, Multicentre Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations, and Whose Disease Has Progressed On or After Prior Anti-PD-(L)1 Therapy and Platinum-based Chemotherapy: LATIFY
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 594
- 试验地点
- 192
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This study will assess the efficacy and safety of the combination of ceralasertib and durvalumab versus standard of care docetaxel in patients with locally advanced and metastatic NSCLC after progression on prior anti-PD-(L)1 therapy and platinum-based chemotherapy.
详细描述
This study will consist of two treatment arms (Groups A and B).
Participants will be randomised in a 1:1 ratio to one of the two treatment groups:
- Group A: Ceralasertib plus durvalumab combination therapy Each 28-day cycle will begin with ceralasertib administered orally followed by durvalumab administered intravenously.
- Group B: Docetaxel monotherapy Each 21-day cycle will begin with the administration of docetaxel.
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
- None
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
- •Histologically or cytologically documented NSCLC that is locally advanced or metastatic according to Version 8 of the IASLC Staging Manual in Thoracic Oncology.
- •Documented epidermal growth receptor factor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type status as determined at a local laboratory.
- •Documented radiological PD whilst on or after receiving the most recent treatment regimen.
- •Eligible for second- or third-line therapy and must have received an anti-PD-(L)1 therapy and a platinum doublet containing therapy for locally advanced or metastatic NSCLC either separately or in combination.
- •Eastern Cooperative Oncology Group (ECOG)/World Health Organization (WHO) performance status of 0 or
- •Adequate organ function and marrow reserve
- •Minimum life expectancy of 12 weeks.
- •Body weight > 30 kg and no cancer-associated cachexia.
- •Negative pregnancy test (serum test) for women of childbearing potential (WOCBP).
排除标准
- •Participant with mixed SCLC and NSCLC histology.
- •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.
- •Persistent toxicities (CTCAE Grade > 2) caused by previous anticancer therapy.
- •Active or prior documented autoimmune or inflammatory disorders.
- •Participants who have received more than one line of prior anti-PD-(L)1, either alone or in any combination.
- •Participants:
- •Must not have experienced a toxicity that led to permanent discontinuation of the prior anti-PD(L)1 therapy.
- •All AEs while receiving prior anti-PD(L)1 therapy must have completely resolved.
- •Must not have experienced a Grade ≥ 3 immune-mediated adverse event (imAE) or an immune-related neurologic or ocular AE of any grade while receiving prior anti-PD(L)1 therapy.
- •Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day.
- •Participants who have received more than one prior line of platinum-based chemotherapy in metastatic setting.
- •Participants who have received a prior ataxia telangiectasia and Rad3-related protein (ATR) inhibitor.
研究组 & 干预措施
Group A: Ceralasertib plus durvalumab combination therapy
Participants will be administered ceralasertib orally followed by durvalumab administered intravenously.
干预措施: Durvalumab (Drug)
Group A: Ceralasertib plus durvalumab combination therapy
Participants will be administered ceralasertib orally followed by durvalumab administered intravenously.
干预措施: Ceralasertib (Drug)
Group B: Docetaxel monotherapy
Participants will be administered docetaxel (standard of care) administered intravenously.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Every 3 months (± 1 week) following objective progression of disease (PD) or treatment discontinuation (up to three years)
The superiority of ceralasertib plus durvalumab combination therapy relative to docetaxel will be demonstrated by assessment of OS (HR with 95% CI and p-value) in participants with advanced NSCLC after second- or third-line therapy and without actionable genomic alterations. OS is defined as time from randomisation until the date of death due to any cause.
次要结局
- TTD of physical function(Up to 3 years)
- Plasma concentrations for ceralasertib plus durvalumab combination therapy(Up to 3 years)
- Time to second progression or death (PFS2)(Up to 3 years)
- Progression-Free Survival (PFS)(Up to 3 years)
- Disease Control Rate (DCR)(At Week 18)
- Objective Response Rate (ORR)(Up to 3 years)
- Duration of Response (DoR)(Up to 3 years)
- Time To Response (TTR)(Up to 3 years)
- Time To Deterioration (TTD) of health-related quality of life (QoL)(Up to 3 years)
- Overall Survival (OS) at 12 months(At 12 months)
- Number of participants with Adverse Evens (AEs)(Up to 3 years)