A Phase III, Randomised, Open-label, Multicentre, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin Versus Pembrolizumab in Combination With Platinum-based Chemotherapy for the First-line Treatment of Patients With Locally Advanced or Metastatic NSCLC Without Actionable Genomic Alterations (D926NC00001; AVANZAR)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 1,350
- 试验地点
- 254
- 主要终点
- Overall Survival (OS) in the non-squamous TROP2 biomarker positive population
研究概览
简要总结
This is a Phase III, randomized, open-label, multicenter, global study to compare the efficacy and safety of Datopotamab Deruxtecan (Dato-DXd) in combination with durvalumab and carboplatin compared with pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment of adults with stage IIIB, IIIC, or IV NSCLC without actionable genomic alterations (including sensitizing EGFR mutations, and ALK and ROS1 rearrangements).
详细描述
Participants with locally advanced or metastatic NSCLC without actionable tumor tissue genomic alterations and confirmed to meet all eligibility criteria will be randomized in a 1:1 ratio to Dato-DXd in combination with durvalumab and carboplatin versus pembrolizumab in combination with histology-specific platinum-based chemotherapy as first-line treatment.
The primary objectives of the study are to demonstrate superiority of Dato-DXd in combination with durvalumab and carboplatin relative to pembrolizumab in combination with platinum-based chemotherapy by assessment of the following:
- PFS by BICR in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
- OS in first-line treatment of participants with non-squamous TROP2 biomarker positive locally-advanced or metastatic NSCLC
- PFS by BICR in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC
- OS in first-line treatment of participants with non-squamous locally-advanced or metastatic NSCLC
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
None (Open Label)
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
- •Participants ≥ 18 years at screening
- •Histologically or cytologically documented NSCLC that at the time of randomisation is Stage IIIB or IIIC disease not amenable to surgical resection or definitive chemoradiation or Stage IV metastatic disease
- •Lacks sensitising EGFR tumour tissue mutation and ALK and ROS1 rearrangements and has no documented tumour genomic alterations in NTRK, BRAF, RET, MET or other actionable driver oncogenes with approved and available therapies (actionable genomic alterations).
- •Testing is not required for tumors with squamous histology, with exceptions.
- •ECOG PS of 0 or 1
- •Archival tumour tissue
- •Has adequate bone marrow reserve and organ function within 7 days before randomization
排除标准
- •Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC
- •History of another primary malignancy with exceptions
- •Persistent toxicities caused by previous anti-cancer therapy not yet improved to Grade ≤ 1 or baseline, with exceptions.
- •Spinal cord compression or clinically or radiologically active brain metastases
- •History of leptomeningeal carcinomatosis.
- •Known active or uncontrolled hepatitis B or C virus infection.
- •Uncontrolled or suspected infection requiring IV antibiotics, antivirals, or antifungals.
- •Clinically significant corneal disease
- •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.
研究组 & 干预措施
Dato-DXd + Durvalumab + Carboplatin
Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 1120 mg durvalumab plus carboplatin area under the curve [AUC] 5 mg/mL/minute.
干预措施: Datopotamab deruxtecan (Drug)
Dato-DXd + Durvalumab + Carboplatin
Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 1120 mg durvalumab plus carboplatin area under the curve [AUC] 5 mg/mL/minute.
干预措施: Carboplatin (Drug)
Histologic-specific therapy
Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin.
Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin.
干预措施: Pemetrexed (Drug)
Histologic-specific therapy
Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin.
Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin.
干预措施: Carboplatin (Drug)
Histologic-specific therapy
Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin.
Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin.
干预措施: Cisplatin (Drug)
Histologic-specific therapy
Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin.
Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin.
干预措施: Paclitaxel (Drug)
Histologic-specific therapy
Non-squamous NSCLC participants will be randomized to receive 200 mg pembrolizumab plus 500 mg/m2 pemetrexed plus either AUC 5 mg/mL/minute carboplatin or 75 mg/m2 cisplatin.
Squamous NSCLC participants will be randomized to receive 200 mg of pembrolizumab plus 200 mg/m2 paclitaxel plus AUC 5 or 6 mg/mL/minute carboplatin.
干预措施: Pembrolizumab (Drug)
Dato-DXd + Durvalumab + Carboplatin
Participants will be randomized to receive 6.0mg/kg Dato-DXd plus 1120 mg durvalumab plus carboplatin area under the curve [AUC] 5 mg/mL/minute.
干预措施: Durvalumab (Drug)
结局指标
主要结局
Overall Survival (OS) in the non-squamous TROP2 biomarker positive population
时间窗: Approximately 5 years
OS is defined as the time from randomisation until the date of death due to any cause.
PFS by BICR in the non-squamous population
时间窗: Approximately 3 years
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
OS in the non-squamous population
时间窗: Approximately 5 years
OS is defined as the time from randomisation until the date of death due to any cause.
Progression-Free Survival (PFS) by blinded independent central review (BICR) in the non-squamous TROP2 biomarker positive population
时间窗: Approximately 3 years
PFS is defined as time from randomisation until progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) as assessed by BICR, or death due to any cause.
Progression-Free Survival (PFS) by blinded independent central review (BICR) in the non-squamous TROP2 biomarker positive population
时间窗: Approximately 3 years
PFS is defined as time from randomisation until progression per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) as assessed by BICR, or death due to any cause.
Overall Survival (OS) in the non-squamous TROP2 biomarker positive population
时间窗: Approximately 5 years
OS is defined as the time from randomisation until the date of death due to any cause.
PFS by BICR in the non-squamous population
时间窗: Approximately 3 years
PFS is defined as time from randomisation until progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
OS in the non-squamous population
时间窗: Approximately 5 years
OS is defined as the time from randomisation until the date of death due to any cause.
次要结局
- PFS by BICR in ITT and TROP2 biomarker-defined populations(Approximately 3 years)
- Objective Response Rate (ORR) in ITT, non-squamous and TROP2 biomarker-defined populations(Approximately 5 years)
- Duration of Response (DoR) in ITT, non-squamous and TROP2 biomarker-defined populations(Approximately 5 years)
- PFS by investigator in ITT, non-squamous and TROP2 biomarker-defined populations(Approximately 3 years)
- Pharmacokinetics of Dato-DXd when combined with durvalumab and carboplatin.(Approximately 5 years)
- Anti-Drug Antibody (ADA) for Dato-DXd(Approximately 5 years)
- Time to Second Progression or Death (PFS2) in ITT, non-squamous and TROP2 biomarker-defined populations(Approximately 5 years)
- Clinical Outcome Assessments in ITT, non-squamous and TROP2 biomarker-defined populations(Approximately 5 years)
- PFS by BICR in ITT and TROP2 biomarker-defined populations(Approximately 3 years)
- OS in ITT and TROP2 biomarker-defined populations(Approximately 5 years)
- Objective Response Rate (ORR) in ITT, non-squamous and TROP2 biomarker-defined populations(Approximately 5 years)
- Duration of Response (DoR) in ITT, non-squamous and TROP2 biomarker-defined populations(Approximately 5 years)
- PFS by investigator in ITT, non-squamous and TROP2 biomarker-defined populations(Approximately 3 years)
- Pharmacokinetics of Dato-DXd when combined with durvalumab and carboplatin.(Approximately 5 years)
- Anti-Drug Antibody (ADA) for Dato-DXd(Approximately 5 years)
- Time to Second Progression or Death (PFS2) in ITT, non-squamous and TROP2 biomarker-defined populations(Approximately 5 years)
- Clinical Outcome Assessments in ITT, non-squamous and TROP2 biomarker-defined populations(Approximately 5 years)