A Phase III, Open-label, Sponsor-blind, Randomized Study of Dato-DXd With or Without Osimertinib Versus Platinum-based Doublet Chemotherapy for Participants With EGFR-mutated Locally Advanced or Metastatic Non-small Cell Lung Cancer Whose Disease Has Progressed on Prior Osimertinib Treatment (TROPION-Lung15)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 744
- 试验地点
- 303
- 主要终点
- Progression free Survival (PFS)
研究概览
简要总结
This study will assess the effect of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in terms of progression-free survival (PFS).
详细描述
This is a Phase III, open-label, 3-arm, multicenter study assessing the effects of Dato-DXd in combination with osimertinib or Dato-DXd monotherapy versus platinum-based doublet chemotherapy in participants with epidermal growth factor receptor gene mutation (EGFRm) locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on prior osimertinib treatment.
Participants will be randomized in a 1:1:1 ratio to one of the following intervention groups:
- Dato-DXd + osimertinib combination therapy
- Dato-DXd monotherapy
- Platinum-based doublet chemotherapy
Participants will receive study intervention until Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) -defined radiological progression by the investigator, unacceptable toxicity, or other discontinuation criterion is met.
After study intervention discontinuation, all participants will undergo an end of treatment (EoT) visit within 35 days of discontinuation and will be followed up for safety assessments 28 (+ 7) days after their last dose of study intervention.
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 confirmed non-squamous NSCLC.
- •Must have evidence of documented pre-existing EGFRm information (EGFRm known to be associated with (epidermal growth factor receptor [EGFR] tyrosine kinase inhibitor [TKis] sensitivity [Ex19del, L858R, G719X, S768I, or L861Q], either alone or in combination with other EGFR mutations, which may include T790M).
- •Documented extra-cranial radiologic progression on prior osimertinib monotherapy (as most recent line of treatment) in the adjuvant, locally advanced, or metastatic setting.
- •Less than or equal to (<=2) prior lines of EGFR TKIs (osimertinib is the only permitted prior third generation EGFR TKI).
- •At least one lesion, not previously irradiated, that qualifies as a RECIST v1.1 TL at baseline and can be accurately measured at baseline.
- •World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate bone marrow reserve and organ function within 7 days before randomization.
排除标准
- •Use of chemotherapy, vascular endothelial growth factor inhibitor, immunotherapy or any anti-cancer therapy in the metastatic setting. Platinum-based chemotherapy in non-metastatic setting within 12 months prior to randomization.
- •History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 2 years before the first dose of study intervention.
- •Any evidence of severe or uncontrolled systemic diseases, including, but not limited to active bleeding diseases, active infection, active ILD/pneumonitis, cardiac disease.
- •Has significant third-space fluid retention (example [eg.], ascites or pleural effusion) as judged by the investigator and is not amenable for required repeated drainage.
- •History of non-infectious ILD/pneumonitis including radiation pneumonitis that required steroids or drug-induced ILD, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
- •Has severe pulmonary function compromise resulting from intercurrent pulmonary illnesses.
- •Unstable spinal cord compression and/or unstable brain metastases.
- •Participants with symptomatic brain metastases (including leptomeningeal involvement).
- •Clinically significant corneal disease.
- •Uncontrolled infection requiring systemic antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections. Use of systemic antibiotics within 14 days of randomization.
- •Has known human immunodeficiency virus (HIV) infection that is not well controlled.
研究组 & 干预措施
Group 1: Dato-DXd + Osimertinib Combination Therapy
Participants will receive Dato-DXd 6 milligrams per kilogram (mg/kg) as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of every 21-day cycle, and osimertinib 80 milligrams (mg) once daily (QD) orally, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met.
干预措施: Dato-DXd (Drug)
Group 1: Dato-DXd + Osimertinib Combination Therapy
Participants will receive Dato-DXd 6 milligrams per kilogram (mg/kg) as intravenous (IV) infusion every 3 weeks (Q3W) on Day 1 of every 21-day cycle, and osimertinib 80 milligrams (mg) once daily (QD) orally, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met.
干预措施: Osimertinib (Drug)
Group 2: Dato-DXd Monotherapy
Participants will receive Dato-DXd 6 mg/kg as IV infusion Q3W on Day 1 of every 21-day cycle, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or other discontinuation criterion is met.
干预措施: Dato-DXd (Drug)
Group 3: Platinum-based Doublet Chemotherapy
Participants will receive pemetrexed 500 milligrams per meter square (mg/m2) in combination with carboplatin (AUC5) or cisplatin 75 mg/m2 as IV infusion Q3W for 4 cycles followed by pemetrexed maintenance 500 mg/m2 as IV infusion Q3W, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or another discontinuation criterion is met.
干预措施: Pemetrexed (Drug)
Group 3: Platinum-based Doublet Chemotherapy
Participants will receive pemetrexed 500 milligrams per meter square (mg/m2) in combination with carboplatin (AUC5) or cisplatin 75 mg/m2 as IV infusion Q3W for 4 cycles followed by pemetrexed maintenance 500 mg/m2 as IV infusion Q3W, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or another discontinuation criterion is met.
干预措施: Carboplatin (Drug)
Group 3: Platinum-based Doublet Chemotherapy
Participants will receive pemetrexed 500 milligrams per meter square (mg/m2) in combination with carboplatin (AUC5) or cisplatin 75 mg/m2 as IV infusion Q3W for 4 cycles followed by pemetrexed maintenance 500 mg/m2 as IV infusion Q3W, until RECIST v1.1-defined radiological progression by investigator, unacceptable toxicity, or another discontinuation criterion is met.
干预措施: Cisplatin (Drug)
结局指标
主要结局
Progression free Survival (PFS)
时间窗: Up to 2.5 years
PFS is defined as the time from randomization to Blinded Independent Central Review (BICR)-assessed progression using RECIST v1.1 or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinical progression.
次要结局
- Overall Survival (OS)(Up to 3.5 years)
- Central Nervous System Progression-free Survival (CNS PFS)(Up to 2.5 years)
- Objective Response Rate (ORR)(Up to 2.5 years)
- Duration of Response (DoR)(Up to 2.5 years)
- Progression-free Survival-2 (PFS-2)(Up to 3.5 years)
- Objective Response Rate (ORR) Using CNS Modified RECIST v1.1(Up to 2.5 years)
- Duration of Response (DoR) Using CNS Modified RECIST v1.1(Up to 2.5 years)
- Time to Deterioration in Pulmonary Symptoms(Up to 3.5 years)
- Time to Deterioration in Physical Functioning(Up to 3.5 years)
- Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL)(Up to 3.5 years)
- Pharmacokinetics (PK) of Dato-DXd(Up to 3.5 years)
- Immunogenicity of Dato-DXd(Up to 3.5 years)
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB