A Phase III, Randomised, Open-label, Global Study of Adjuvant Datopotamab Deruxtecan (Dato-DXd) in Combination With Rilvegostomig or Rilvegostomig Monotherapy Versus Standard of Care, Following Complete Tumour Resection, in Participants With Stage I Adenocarcinoma Non-small Cell Lung Cancer Who Are ctDNA-positive or Have High-risk Pathological Features (TROPION-Lung12)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 25
- 试验地点
- 90
- 主要终点
- Disease-Free Survival (DFS) using BICR in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive or having at least one high-risk pathological feature treated with adjuvant Dato-DXd in combination with rilvegostomig relative to SoC
研究概览
简要总结
This is a Phase III, randomised, open-label, multicentre, global study assessing the efficacy and safety of adjuvant Dato-DXd in combination with rilvegostomig compared with SoC, after complete surgical resection (R0) in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive, as determined by the Sponsor-designated ctDNA assay, or have at least one high-risk pathological feature.
详细描述
The primary objective of the study is to assess the efficacy and safety of adjuvant Dato-DXd in combination with rilvegostomig relative to SoC, after complete surgical resection (R0) in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive, as determined by the Sponsor-designated ctDNA assay, or have at least one high-risk pathological feature.
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
- Single (Outcomes Assessor)
盲法说明
Open-label, sponsor-blinded
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
- •Histologically documented treatment-naive Stage I (T < 4 cm, AJCC 8th ed) adenocarcinoma NSCLC
- •Complete surgical resection (R0) of the primary NSCLC
- •Unequivocal no evidence of disease at post-surgical
- •Pre-surgical ctDNA-positive result (Stage IA or IB) OR presence of at least one high-risk pathological feature (visceral pleural invasion (VPI), lymphovascular invasion (LVI), high-grade histology) (Stage IB only)
- •ECOG of 0 or 1, life expectancy of > 6 months and complete recovery after surgery
- •Adequate bone marrow reserve and organ function
排除标准
- •Sensitizing EGFR mutation and/or ALK alteration
- •History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening
- •Significant pulmonary function compromise
- •History of another primary malignancy within 3 years (with exceptions)
- •Any evidence of severe or uncontrolled systemic diseases, including but not limited to bleeding diseases, active infection and cardiac disease
- •Active or prior documented autoimmune or inflammatory disorders (with exceptions)
- •Active infection with tuberculosis, hepatitis B or C virus, hepatitis A, or known HIV infection that is not well controlled
- •History of active primary immunodeficiency
- •Clinically significant corneal disease
研究组 & 干预措施
Dato-DXd + rilvegostomig
Participants in the Dato-DXd in combination with rilvegostomig group will receive Dato-DXd and rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W).
干预措施: Datopotamab Deruxtecan (Drug)
Standard of Care (SoC)
Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).
干预措施: Carboplatin (Drug)
Dato-DXd + rilvegostomig
Participants in the Dato-DXd in combination with rilvegostomig group will receive Dato-DXd and rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W).
干预措施: Rilvegostomig (Drug)
Rilvegostomig
Participants in the rilvegostomig monotherapy group will receive rilvegostomig as intravenous (IV) infusion every 3 weeks (Q3W).
干预措施: Rilvegostomig (Drug)
Standard of Care (SoC)
Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).
干预措施: Cisplatin (Drug)
Standard of Care (SoC)
Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).
干预措施: Etoposide (Drug)
Standard of Care (SoC)
Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).
干预措施: Pemetrexed (Drug)
Standard of Care (SoC)
Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).
干预措施: Vinorelbine (Drug)
Standard of Care (SoC)
Patients in SoC group will undergo observation or will receive Investigator's Choice of Chemotherapy (ICC).
干预措施: UFT (Drug)
结局指标
主要结局
Disease-Free Survival (DFS) using BICR in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive or having at least one high-risk pathological feature treated with adjuvant Dato-DXd in combination with rilvegostomig relative to SoC
时间窗: From date of randomisation up to approximately 10 years.
The analysis will include all randomised participants as randomised. All events will be included, regardless of whether the participant withdraws from randomised therapy or receives another anti-cancer therapy. The measure of interest is the HR of DFS. Descriptive analyses of Dato-DXd in combination with rilvegostomig versus rilvegostomig monotherapy and rilvegostomig monotherapy versus SoC will be performed to assess contribution of components.
次要结局
- Overall Survival (OS) in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive or having at least one high-risk pathological feature treated with adjuvant Dato-DXd in combination with rilvegostomig relative to SoC(From date of randomisation up to approximately 10 years.)
- Participant-reported physical function in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive or having at least one high-risk pathological feature treated with adjuvant Dato-DXd in combination with rilvegostomig relative to SoC(Measured at weeks 12, 24 and 48.)
- Participant-reported GHS/QoL in participants with Stage I adenocarcinoma NSCLC who are ctDNA-positive or having at least one high-risk pathological feature treated with adjuvant Dato-DXd in combination with rilvegostomig relative to SoC(Measured at weeks 12, 24 and 48.)
- Immunogenicity(Up to 30 or 90 days post-last dose of study intervention.)
- Pharmacokinetics (PK)(Up to 30 or 90 days post-last dose of study intervention.)