A Phase 3, Multicenter, Randomized, Open-label Trial of Trastuzumab Deruxtecan in Combination With Pembrolizumab Versus Platinum-based Chemotherapy in Combination With Pembrolizumab, as First-line Therapy in Participants With Locally Advanced Unresectable or Metastatic HER2 Overexpressing and PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer (DESTINY-Lung06)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 686
- 试验地点
- 296
- 主要终点
- Progression Free Survival by Blinded Independent Central Review
研究概览
简要总结
This clinical trial is designed to assess the efficacy and safety of trastuzumab deruxtecan (T-DXd; Enhertu®) in combination with pembrolizumab versus platinum-based chemotherapy in combination with pembrolizumab in participants with no prior therapy for locally advanced unresectable or metastatic non-squamous NSCLC, whose tumors have HER2-overexpressing and PD-L1 TPS <50% without known AGA that have locally available therapies targeting their AGAs in first-line advanced/metastatic setting.
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
盲法说明
This is an open-label study.
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
- •Sign and date the Tissue Screening ICF, prior to any Tissue Screening procedure. Sign and date the Main ICF, prior to the start of any trial-specific qualification procedures.
- •Sign and date the Optional PGx ICF (included in the Main ICF) prior to any PGx procedure, and the Pregnant Partner ICF, if applicable.
- •Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory requirements if the legal age of consent for trial participation is >18 years old.
- •Histologically documented non-squamous locally advanced unresectable or metastatic
- •NSCLC and meets all of the following criteria:
- •Has Stage IV NSCLC disease or Stage IIIB or IIIC disease but is not a candidate for surgical resection or definitive chemoradiation at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition). Has no known AGAs (based on the local test results obtained using validated or approved tests as required per local regulation) that have locally available therapies targeting their AGAs in the first-line advanced/metastatic setting.
- •Has no known HER2 mutation based on existing test results (if approved or validated local test is available). Note: Participants with mixed histology are eligible if non-squamous NSCLC is the predominant histology. Mixed tumors will be classified based on the predominant cell type.
- •Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC. Participants who received adjuvant or neoadjuvant therapy other than those listed below, including ICI (ie, anti-PD-1/PD-L1) or a platinum-based regimen, are eligible if the last dose of adjuvant/neoadjuvant therapy was given at least 6 months before the date of the first trial dose if their disease has progressed at least 6 months after the last dose date of adjuvant/neoadjuvant therapy.
- •Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I.
- •HER2-targeted antibody-based anticancer therapy.
- •Has adequate tumor tissue sample (not previously irradiated) available for assessment of HER2 and PD-L1 expression by central or Sponsor-specified laboratory. A new biopsy is required if the participant's most recent archival tumor tissue sample cannot be supplied.
- •Details pertaining to tumor tissue submission can be found in the Trial Laboratory Manual.
排除标准
- •Has a medical history of MI within 6 months before randomization/enrollment or symptomatic CHF (NYHA Class II to Class IV). Participants with troponin levels above the ULN at Screening (as defined by the manufacturer) and without any MI-related symptoms must be ruled out for MI. It is highly recommended that the investigator refer such participants for a cardiologic consultation during the Screening Period.
- •Has a QTc prolongation to >480 ms based on the average of the Screening triplicate 12- lead ECG.
- •Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- •Has clinically severe pulmonary compromise resulting from intercurrent, pulmonary illnesses including, but not limited to:
- •Any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the trial randomization, severe asthma, severe COPD, restrictive lung disease, pleural effusion).
- •Any auto immune, connective tissue, or inflammatory disorders with potential pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis).
- •Severe conditions are those defined as impacting daily activities and/or requiring use of supplemental oxygen.
- •Had a prior complete pneumonectomy.
研究组 & 干预措施
Arm B: Pemetrexed + Platinum Chemotherapy + Pembrolizumab
Participants will receive Pemetrexed plus platinum chemotherapy (cisplatin or carboplatin) plus pembrolizumab
干预措施: Pemetrexed (Drug)
Arm A: T-DXd + Pembrolizumab
Participants will receive T-DXd plus pembrolizumab
干预措施: Trastuzumab Deruxtecan (Drug)
Arm B: Pemetrexed + Platinum Chemotherapy + Pembrolizumab
Participants will receive Pemetrexed plus platinum chemotherapy (cisplatin or carboplatin) plus pembrolizumab
干预措施: pembrolizumab (Drug)
Arm B: Pemetrexed + Platinum Chemotherapy + Pembrolizumab
Participants will receive Pemetrexed plus platinum chemotherapy (cisplatin or carboplatin) plus pembrolizumab
干预措施: Platinum Chemotherapy (Drug)
Arm A: T-DXd + Pembrolizumab
Participants will receive T-DXd plus pembrolizumab
干预措施: pembrolizumab (Drug)
结局指标
主要结局
Progression Free Survival by Blinded Independent Central Review
时间窗: From date of randomization to the date of radiographic disease progression or death due to any cause, up to 54 months
PFS is defined as the time interval from the date of randomization to the date of radiographic disease progression or death due to any cause. Tumor response will be determined by BICR assessment of tumor scans using RECIST v1.1.
Progression Free Survival by Blinded Independent Central Review
时间窗: From date of randomization to the date of radiographic disease progression or death due to any cause, up to approximately 54 months
PFS is defined as the time interval from the date of randomization to the date of radiographic disease progression or death due to any cause. Tumor response will be determined by BICR assessment of tumor scans using RECIST v1.1.
次要结局
- Overall Survival(From date of randomization to the date of death due to any cause, up to 85 months)
- Overall Survival(From date of randomization to the date of death due to any cause, up to approximately 85 months)