CTRI/2025/02/080765招募中3 期
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
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 630
- 试验地点
- 13
- 主要终点
- Progression free Survival (PFS)
研究概览
简要总结
This is a Phase III, open-label, sponsor-blind, randomized, 3-arm, multicenter study assessing the effects of Dato-DXd monotherapy and Dato-DXd in combination with osimertinib versus platinum-based doublet chemotherapy in participants with EGFRm locally advanced or metastatic NSCLC whose disease has progressed on prior osimertinib treatment. The study will be conducted at approximately 280 sites globally across an estimated 26 countries. The proposed dual primary objectives are to demonstrate the superiority of Dato-DXd with and without osimertinib compared to chemotherapy in terms of PFS assessed by BICR. Key secondary efficacy endpoints are OS and CNS PFS. The safety and tolerability profile of Dato-DXd with or without osimertinib versus chemotherapy will also be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
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 Ex19de, 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 less than 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 IV antibiotics, antivirals, or antifungals, suspected infections or inability to rule out infections.
- •Has known human immunodeficiency virus (HIV) infection that is not well controlled.
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.
时间窗: Up to 2.5 years.
次要结局
- Overall Survival (OS)(OS is defined as time from randomization until the date of death due to any cause.)
- Central Nervous System Progression-free Survival (CNS PFS)(CNS PFS is defined as the time from randomization to BICR confirmed progression in the CNS or death due to any cause, regardless of whether the participant withdraws from study therapy, receives other anti-cancer therapy, or clinically progresses prior to BICR confirmed CNS modified RECIST v1.1 progression.)
- Objective Response Rate (ORR)(ORR is defined as the percentage of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by BICR per RECIST v1.1.)
- Duration of Response (DoR)(DoR is defined as the time from the date of first documented response until date of documented progression per RECIST v1.1, as assessed by BICR or death due to any cause.)
- Progression-free Survival-2 (PFS-2)(PFS2 is defined as the time from randomization to the earliest of the progression event (following the initial investigator assessed progression), after first subsequent therapy, or death.)
- Objective Response Rate (ORR) Using CNS Modified RECIST v1.1(ORR is defined as the percentage of participants who have a confirmed CR or confirmed PR, using CNS modified RECIST v1.1.)
- Duration of Response (DoR) Using CNS Modified RECIST v1.1(DoR is defined as the time from the date of first documented response until date of documented progression or death due to any cause using CNS modified RECIST v1.1.)
- Time to Deterioration in Pulmonary Symptoms(Time to deterioration (in pulmonary symptoms [dyspnea, cough, and chest pain]) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.)
- Time to Deterioration in Physical Functioning(Time to deterioration in physical functioning as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function short form 8c will be evaluated. Time to deterioration (in physical functionating) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.)
- Time to Deterioration in Global Health Status (GHS)/Quality of Life (QoL)(Time to deterioration in GHS/QoL as measured by the GHS/QoL scale from EORTC IL172 will be reported. Time to deterioration (in GHS/QoL) is defined as the time from randomization until the date of deterioration. Deterioration is defined as change from baseline that reaches a meaningful change threshold.)
- Pharmacokinetics (PK) of Dato-DXd(Concentration of Dato-DXd, total anti-TROP2 antibody and DXd in plasma.)
- Immunogenicity of Dato-DXd(Presence of antidrug antibody (ADAs) for Dato-DXd (confirmatory results: positive or negative, titers))
研究者
研究点 (13)
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