A Multicentre, Phase II, Single-Arm, Interventional Study of Neoadjuvant Durvalumab and Platinum-based Chemotherapy (CT), Followed by Either Surgery and Adjuvant Durvalumab or Chemoradiotherapy (CRT) and Consolidation Durvalumab, in Participants With Resectable or Borderline Resectable Stage IIB-IIIB Non-small Cell Lung Cancer (NSCLC)
概览
- 阶段
- 2 期
- 干预措施
- Durvalumab
- 疾病 / 适应症
- Non-small Cell Lung Cancer
- 发起方
- AstraZeneca
- 入组人数
- 142
- 试验地点
- 51
- 主要终点
- Resection rate
- 状态
- 进行中（未招募）
- 最后更新
- 16天前
概览
简要总结
The purpose of this study is to assess efficacy and safety of neoadjuvant durvalumab in combination with platinum-based chemotherapy (CT) given as initial therapy after cancer diagnosis followed by either surgery and adjuvant durvalumab or chemoradiotherapy (CRT) and consolidation durvalumab given alone as further therapy in participants with resectable and borderline resectable stage IIB-IIIB NSCLC.
详细描述
This will be a multicentre, Phase II, single-arm, global study assessing the efficacy and safety of neoadjuvant durvalumab and platinum-based CT, given intravenously, followed by either surgery and adjuvant durvalumab or definitive CRT and consolidation durvalumab in participants with resectable and borderline resectable stage IIB-IIIB NSCLC. Neoadjuvant Period A: All participants will initially receive 2 cycles of neoadjuvant durvalumab + CT (investigator's choice platinum-based) every three weeks. Participants will be assessed for resectability by a multidisciplinary team. Neoadjuvant Period B: Cohort 1: Participants who are deemed eligible for surgery will receive study intervention every three weeks for an additional one and up to two cycles, followed by surgery. CRT: Cohort 2: Participants with unresectable tumours (according to MDT re-assessment) will receive definitive CRT (6 one-week cycles) for approximately six weeks. Both cohorts will then go on to receive durvalumab every four weeks until disease progression or recurrence or up to one year.
研究者
入排标准
入选标准
- •Deemed resectable or borderline resectable at baseline, confirmed by MDT evaluation at diagnosis.
- •Previously untreated and pathologically confirmed Stage IIB to select \[i.e.N2\] Stage IIIB by AJCC v
- •Nodal status confirmed with whole body FDG-PET and biopsy via endobronchial ultrasound, mediastinoscopy, or thoracoscopy.
- •Mandatory brain MRI.
- •EGFR and ALK wild-type.
- •Medically operable: adequate cardiac and lung function to undergo resection.
- •Participant must be ≥ 18 years, at the time of screening.
- •Histologically or cytologically documented NSCLC.
- •Minimum life expectancy of 12 weeks.
- •Minimum body weight of 30 kg.
排除标准
- •Unresectable NSCLC confirmed by MDT evaluation at baseline
- •Stage IIIC patients
- •Participants whose planned surgery at enrollment is a wedge resection
- •Known EGFR mutation or ALK translocation
- •Participants contraindicated for surgical intervention due to comorbid conditions
- •Participants who are allergic to study intervention.
- •Participants with more than one primary tumour.
- •Known active hepatitis infection, positive HCV antibody, HBsAg or HBV core antibody (anti-HBc), at screening.
- •Female participants who are pregnant or breastfeeding.
- •Judgement by the investigator that the participant should not participate in the study.
研究组 & 干预措施
Durvalumab
Durvalumab will be administered to the participants via intravenous infusion (IV)
干预措施: Durvalumab
结局指标
主要结局
Resection rate
时间窗: At day of surgery (Within 40 days of the last dose of neoadjuvant treatment)
Resection rate is defined as the proportion of all participants who underwent definitive surgery. Participants who undergo (ie, start) surgery with the goal of complete tumour resection will be counted as meeting this endpoint.
次要结局
- Resection rate(At the day of surgery (within 40 days after the last dose of neoadjuvant treatment))
- R0, R1, R2 resection rates(At the day of surgery (within 40 days after the last dose of neoadjuvant treatment))
- Pathological complete response (pCR)(At the day of surgery (within 40 days after the last dose of neoadjuvant treatment))
- Overall Survival (OS)(From first dose of study intervention until death, withdrawal of consent, or the end of the study (approximately 3.5 years))
- Overall Survival (OS) rate(At 12 months and 24 months)
- Event-free survival (EFS)(From first dose of study intervention until progression of disease (PD), recurrence or death, withdrawal of consent, or the end of the study (approximately 3.5 years))
- Event-free survival (EFS) rate(At 12 months and 24 months)
- Progression Free Survival (PFS)(From first dose of study intervention until disease progression, death, withdrawal of consent, or the end of the study (approximately 3.5 years))
- Progression Free Survival (PFS) rate(At 12 months and 24 months)
- Objective response rate (ORR) pre-surgery/pre-chemoradiotherapy (CRT)(From first dose of study intervention until death, surgery/start of CRT)
- ORR during study intervention and definitive CRT(From MDT re-assessment timepoint (baseline for this endpoint) until the first tumour assessment after definitive CRT)
- Surgical safety: Duration of surgical procedure(Time from start of surgery to end of surgery)
- Surgical safety: Length of post operative hospital stay(Time from the beginning of the surgery/procedure to the discharge of hospital)
- Surgical safety: Intended surgical approach(At baseline)
- Percentage of all participants with circulating tumor DNA (ctDNA) clearance(From Cycle 1 Day 1 up to pre-surgery/CRT (within 7 to 14 days pre-surgery/CRT) [Each cycle is of 3 weeks])
- Number of participants with adverse events(From enrollment up to at least 90 days after last dose of study intervention)
- Surgical safety: Actual surgical approach(At surgery)
- Surgical safety: Intended surgical procedure(At baseline)
- Surgical safety: Actual surgical procedure(At surgery)
- Number of participants with delayed surgery(40 days after last dose of study intervention to surgery)
- Surgical safety: Length of surgical delays(40 days after last dose of study intervention to surgery)
- Number of participants with reason of surgical delay(40 days after last dose of study intervention to surgery)
- Time from last neoadjuvant dose to surgery(Time from last neoadjuvant dose of study intervention to surgery)