A Phase II Study of SKB264 as Monotherapy or as Combination Therapy in Subjects With Advanced or Metastatic Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 356
- 试验地点
- 104
- 主要终点
- Safety and tolerability
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability and objective response rate of SKB264 as combination with therapy in subjects with advanced or metastatic non-small cell lung cancer.
详细描述
This is a multicenter, open-label study of SKB264 as combination therapy or monotherapy in subjects with NSCLC. Approximately 498 subjects will be enrolled in this study including around 88 subjects for the safety run-in period and 410 subjects for the expansion period.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be at least 18 years of age on day of signing informed consent, regardless of gender;
- •Subjects with histologically or cytologically confirmed locally advanced or metastatic NSCLC ;
- •Subjects for NSCLC should be confirmed to be EGFR (Epidermal growth factor receptor) wild-type and ALK (Anaplastic lymphoma kinase) fusion gene negative; or confirmed to harbor EGFR mutation;
- •Locally advanced or metastatic NSCLC subjects without actionable EGFR mutations and ALK fusion genes, no prior systemic treatment; subjects with EGFR mutation, no prior systemic treatment or failed prior EGFR-TKI (Tyrosine kinase inhibitor) treatment;
- •Subjects are able to provide tumor blocks or slides before the first dose of study intervention;
- •Subject must have at least one radiographically measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria;
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1;
- •Life expectancy at least 3 months for the subject;
- •Adequate organ function;
- •Subjects must have recovered from all toxicities led by prior treatment;
- •Contraceptive methods used by male and female subjects must comply with contraceptive methods of local regulations for clinical study subjects;
- •Subjects should voluntarily participate in the study, sign the ICF, and will be able to comply with the protocol-specified visits and relevant procedures.
排除标准
- •Subjects with mixed SCLC histopathological features;
- •Subjects with a known history of prior malignancy;
- •Subjects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression, or active central nervous system (CNS) metastases;
- •Subjects with ≥ Grade 2 peripheral neuropathy;
- •Subjects who had arteriovenous thromboembolic events, tumor invasion/encasement of vital organs/vessels, risk of esophageal-tracheal/pleural fistula, or current superior vena cava syndrome;
- •Subjects with active inflammatory bowel disease or previous clear history of inflammatory bowel disease;
- •Subjects who suffer from cardiovascular diseases of clinical significance;
- •Subjects with a history of interstitial lung disease (ILD)/non-infectious pneumonitis that required steroids;
- •Subjects with uncontrolled systemic disease as judged by the Investigator;
- •Subjects with active autoimmune disease that required systemic treatment in the past 2 years;
- •Subjects with active hepatitis B or hepatitis C;
- •Subjects with known history of Human Immunodeficiency Virus (HIV)
- •Subjects with known active tuberculosis;
- •Subjects with known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
- •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study;
- •Subjects whose condition deteriorated rapidly, such as severe changes in performance status, during the screening process prior to the first dose of study intervention;
- •Subjects with other circumstances that, in the opinion of the Investigator, are not appropriate for participation in this study.
研究组 & 干预措施
Cohort 1 1L NSCLC, EGFR/ALK negative and PD-L1 TPS ≥ 1%
SKB264 (Dose Level 1) + Pembrolizumab
干预措施: SKB264 (Drug)
Cohort 1 1L NSCLC, EGFR/ALK negative and PD-L1 TPS ≥ 1%
SKB264 (Dose Level 1) + Pembrolizumab
干预措施: Pembrolizumab (Drug)
Cohort 3 1L NSCLC, EGFR/ALK negative, regardless of PD-L1 expression level
SKB264 (Dose Level 1') + Pembrolizumab + Carboplatin
干预措施: SKB264 (Drug)
Cohort 3 1L NSCLC, EGFR/ALK negative, regardless of PD-L1 expression level
SKB264 (Dose Level 1') + Pembrolizumab + Carboplatin
干预措施: Pembrolizumab (Drug)
Cohort 3 1L NSCLC, EGFR/ALK negative, regardless of PD-L1 expression level
SKB264 (Dose Level 1') + Pembrolizumab + Carboplatin
干预措施: Carboplatin (Drug)
Cohort 4 1L NSCLC, EGFR/ALK negative, regardless of PD-L1 expression level
SKB264 (Dose Level 1'') + Pembrolizumab + Carboplatin
干预措施: SKB264 (Drug)
Cohort 4 1L NSCLC, EGFR/ALK negative, regardless of PD-L1 expression level
SKB264 (Dose Level 1'') + Pembrolizumab + Carboplatin
干预措施: Pembrolizumab (Drug)
Cohort 4 1L NSCLC, EGFR/ALK negative, regardless of PD-L1 expression level
SKB264 (Dose Level 1'') + Pembrolizumab + Carboplatin
干预措施: Carboplatin (Drug)
Cohort 5 NSCLC with EGFR mutation and after failure of EGFR TKI therapy
SKB264 (Dose Level 1') + Carboplatin
干预措施: SKB264 (Drug)
Cohort 5 NSCLC with EGFR mutation and after failure of EGFR TKI therapy
SKB264 (Dose Level 1') + Carboplatin
干预措施: Carboplatin (Drug)
Cohort 6 NSCLC with EGFR mutation and after failure of EGFR TKI therapy
SKB264 (Dose Level 1'') + Carboplatin
干预措施: SKB264 (Drug)
Cohort 6 NSCLC with EGFR mutation and after failure of EGFR TKI therapy
SKB264 (Dose Level 1'') + Carboplatin
干预措施: Carboplatin (Drug)
Cohort 7 1L NSCLC with EGFR mutation
SKB264 (Dose Level 1) + Osimertinib
干预措施: SKB264 (Drug)
Cohort 7 1L NSCLC with EGFR mutation
SKB264 (Dose Level 1) + Osimertinib
干预措施: Osimertinib (Drug)
Cohort 7-1 1L NSCLC with EGFR mutation
SKB264 (Dose Level 2) + Osimertinib
干预措施: SKB264 (Drug)
Cohort 7-1 1L NSCLC with EGFR mutation
SKB264 (Dose Level 2) + Osimertinib
干预措施: Osimertinib (Drug)
Cohort 9 2/3L NSCLC EGFR/ALK negative
SKB264 (Dose Level 1)
干预措施: SKB264 (Drug)
结局指标
主要结局
Safety and tolerability
时间窗: From subject sign the informed consent form (ICF) to 30 days after the last dose of study treatment, up to approximately 36 months
Dose-limiting toxicity (DLT); Incidence and severity of adverse events (AEs); Discontinuation of study treatment due to AEs
ORR
时间窗: The proportion of subjects with a confirmed complete response (CR) or partial response (PR), up to approximately 36 months
Objective response rate (ORR) per RECIST v1.1
次要结局
- Duration of response (DOR)(From baseline until disease progression, death, or other protocol defined reason, up to approximately 36 months)
- Progression-free survival (PFS)(From baseline until disease progression, death, or other protocol defined reason, up to approximately 36 months)
- Overall survival (OS)(From baseline until death due to any cause, up to approximately 36 months)