A Randomized, Open-Label, Multicenter Phase 3 Clinical Study of SKB264 in Combination With Pembrolizumab Versus Chemotherapy in Combination With Pembrolizumab as First-Line Treatment for PD-L1 Negative Patients With Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 432
- 试验地点
- 82
- 主要终点
- Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR)
研究概览
简要总结
The study aims to evaluate the efficacy and safety of SKB264 in combination with pembrolizumab versus chemotherapy in combination with pembrolizumab in the first-line treatment of patients with locally advanced or metastatic non-squamous NSCLC with PD-L1 negative.
详细描述
This is a randomized, open-label, multicenter, Phase 3 study to evaluate the efficacy and safety of SKB264 in combination with pembrolizumab versus chemotherapy in combination with pembrolizumab in the first-line treatment of patients with locally advanced or metastatic non-squamous NSCLC with PD-L1 negative.
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 75 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, and unsuitable for radical surgery and/or radical concurrent/sequential radiochemotherapy, locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) NSCLC;
- •EGFR-sensitive mutation negative [no exon 19 deletion (19-Del) or exon 21 point mutation (L858R mutation)] and ALK fusion gene negative, without known ROS1 gene fusion, NTRK gene fusion, BRAF V600E mutation, etc. that have been approved for targeted therapy driving gene alterations;
- •No prior systemic anti-cancer therapy for locally advanced or metastatic NSCLC;
- •Participants whose tumours are PD-L1 TPS < 1%;
- •At least one measurable lesion per RECIST v1.1;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with no worsening within 7 days prior to randomization;
- •A life expectancy of at least 12 weeks;
- •Adequate organ and bone marrow function;
排除标准
- •Histologically or cytologically confirmed tumors with a component of small cell lung cancer, neuroendocrine carcinoma, sarcomatoid carcinoma, or squamous cell carcinoma exceeding 10%;
- •Previously received immune checkpoint inhibitors,checkpoint agonists or any treatment targeting the immune mechanism of tumors such as immune cell therapy;
- •Active second malignancy;
- •Symptomatic or uncontrolled cardiovascular disease，serious thromboembolic；
- •History of noninfectious pneumonitis/interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD;
- •Active infection requiring systemic therapy within 2 weeks of randomization;
- •Active hepatitis B or hepatitis C virus infection;
- •Human immunodeficiency virus (HIV) positive or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection;
- •Major surgery within 4 weeks prior to randomization or expected major surgery during the study;
- •Pregnant or lactating women;
研究组 & 干预措施
SKB264+Pembrolizumab
Participants will receive SKB264 on Day 1、Day 15 and Day 29 of each 6-week cycle,Pembrolizumab on Day1 of each 6-week cycle.
干预措施: SKB264 (Drug)
SKB264+Pembrolizumab
Participants will receive SKB264 on Day 1、Day 15 and Day 29 of each 6-week cycle,Pembrolizumab on Day1 of each 6-week cycle.
干预措施: Pembrolizumab (Drug)
Pembrolizumab+Chemotherapy
Participants will receive Pembrolizumab on Day1 of each 6-week cycle,Chemotherapy on Day1 and Day 22 of each 6-week
干预措施: Pembrolizumab (Drug)
Pembrolizumab+Chemotherapy
Participants will receive Pembrolizumab on Day1 of each 6-week cycle,Chemotherapy on Day1 and Day 22 of each 6-week
干预措施: pemetrexed (Drug)
Pembrolizumab+Chemotherapy
Participants will receive Pembrolizumab on Day1 of each 6-week cycle,Chemotherapy on Day1 and Day 22 of each 6-week
干预措施: carboplatin or cisplatin (Drug)
结局指标
主要结局
Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR)
时间窗: Randomization up to approximately 28 months
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first.
次要结局
- Overall Survival (OS)(Randomization up to approximately 43 months)
- Progression-Free Survival (PFS) assessed by Investigator(Randomization up to approximately 28 months)
- Objective Response Rate (ORR)(Randomization up to approximately 28 months)
- Disease control rate (DCR)(Randomization up to approximately 28 months)
- Duration of Response (DoR)(Randomization up to approximately 28 months)
- Time to Response (TTR)(Randomization up to approximately 28 months)
- AEs and SAEs(All AEs should be observed and recorded from the first dose until 30 days after the last dose. SAEs were observed and recorded until 90 days after the last dose of pembrolizumab or 30 days after the last dose of SKB264,whichever occurred later.)
- Health-Related Quality of Life Assessed by EORTC QLQ-C30(Randomization up to approximately 28months)
- Lung Cancer-Related Symptoms Assessed by EORTC QLQ-LC13 Symptom Domain(From randomization up to approximately 28 months)
- PK(Randomization up to approximately 28months)
- Immunogenicity(Randomization up to approximately 28months)
- Biomarkers(Tumor tissue samples should be provided for TROP2 testing after subjects are eligible for screening.)