A Phase Ⅱ Clinical Study of Combination Therapy of SKB264 in Patients With Advanced or Metastatic Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- Incidence and severity of adverse events (AEs)
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability and preliminary antitumor activity of SKB264 in combination with KL-A167 with or without chemotherapy with advanced or metastatic non-small cell lung cancer. The study is divided into two parts. Part 1 will be the safety run-in phase, and Part 2 will be the cohort expansion phase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Males or females ≥ 18 and ≤ 75 years of age at the time of signing the informed consent form;
- •Histologically and cytologically confirmed NSCLC;
- •Cohort 1: Patients with locally advanced/metastatic NSCLC with wild-type EGFR and negative ALK fusion gene, no or at most one prior line of systemic chemotherapy regimen for advanced or metastatic NSCLC. Cohort 2: Patients with locally advanced/metastatic NSCLC with wild-type EGFR and negative ALK fusion gene, no prior systemic therapy. Cohort 3: Patients with locally advanced/metastatic NSCLC with EGFR activating mutation and negative ALK fusion gene, who have failed previous treatment with EGFR-TKIs.
- •Provide fresh or archival tumor tissue for biomarker testing and analysis;
- •Patients with at least one measurable lesion per RECIST v1.1 criteria, and patients with only skin or bone lesions cannot be enrolled;
- •Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with an expected survival of ≥ 12 weeks;
- •Adequate organ and bone marrow function
- •For female patients of childbearing age and male patients with partners of childbearing age, they must use effective medical contraception during the study treatment period and for 6 months after the last dose of study medication (see Annex for specific contraceptive measures);
- •Each patient must voluntarily agree to participate in the study, sign the informed consent form, and comply with the protocol-specified visits and relevant procedures.
排除标准
- •Presence of small cell lung carcinoma (SCLC) components in histological pathology;
- •History of other malignancies;
- •Presence of metastases to brainstem, meninges and spinal cord, or spinal cord compression;
- •Presence of active central nervous system (CNS) metastases;
- •Imaging (CT or MRI) shows that the tumor surrounds important blood vessels, or the investigator determines that the tumor is most likely to invade important blood vessels during the subsequent study to cause fatal major hemorrhage;
- •Serious or uncontrolled cardiac disease or clinical symptoms requiring treatment, including any of the following:
- •Patients with (noninfectious) interstitial lung disease (ILD) or history of pneumonia requiring steroid therapy; patients with serious pulmonary function impairment due to lung disease;
- •Uncontrolled systemic disease as judged by the investigator, included uncontrolled hypertension, uncontrolled diabetes, pesence of pleural effusion, pericardial effusion, or ascites that is clinically symptomatic or requires repeated drainage;
- •Certain viral infections including active hepatitis B or hepatitis C; known history of positive human immunodeficiency virus (HIV) test or known acquired immunodeficiency syndrome (AIDS); or positive syphilis antibody test;
- •Known active tuberculosis;
- •Known hypersensitivity to the study drug or any of its components, or severe allergic reactions to other monoclonal antibodies;
- •Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
- •Pregnant or lactating women;
- •Any patient whose condition deteriorates rapidly during the screening process prior to the first dose, such as severe changes in performance status, unstable pain requiring adjustment of analgesic therapy, etc
- •Other circumstances that, in the opinion of the investigator, are not appropriate for participation in this study.
研究组 & 干预措施
SKB264+KL-A167+ Carboplatin or Cisplatin (EGFR wide type)
Participants received SKB264 followed by KL-A167 with Carboplatin or Cisplatin
干预措施: Cisplatin (Drug)
SKB264+KL-A167
Participants received SKB264 followed by KL-A167
干预措施: SKB264 (Drug)
SKB264+KL-A167
Participants received SKB264 followed by KL-A167
干预措施: KL-A167 (Drug)
SKB264+KL-A167+ Carboplatin or Cisplatin (EGFR wide type)
Participants received SKB264 followed by KL-A167 with Carboplatin or Cisplatin
干预措施: SKB264 (Drug)
SKB264+KL-A167+ Carboplatin or Cisplatin (EGFR wide type)
Participants received SKB264 followed by KL-A167 with Carboplatin or Cisplatin
干预措施: KL-A167 (Drug)
SKB264+KL-A167+ Carboplatin or Cisplatin (EGFR mutation)
Participants received SKB264 followed by KL-A167 with Carboplatin or Cisplatin
干预措施: SKB264 (Drug)
SKB264+KL-A167+ Carboplatin or Cisplatin (EGFR mutation)
Participants received SKB264 followed by KL-A167 with Carboplatin or Cisplatin
干预措施: KL-A167 (Drug)
SKB264+KL-A167+ Carboplatin or Cisplatin (EGFR mutation)
Participants received SKB264 followed by KL-A167 with Carboplatin or Cisplatin
干预措施: Carboplatin (Drug)
SKB264+KL-A167+ Carboplatin or Cisplatin (EGFR wide type)
Participants received SKB264 followed by KL-A167 with Carboplatin or Cisplatin
干预措施: Carboplatin (Drug)
SKB264+KL-A167+ Carboplatin or Cisplatin (EGFR mutation)
Participants received SKB264 followed by KL-A167 with Carboplatin or Cisplatin
干预措施: Cisplatin (Drug)
结局指标
主要结局
Incidence and severity of adverse events (AEs)
时间窗: From baseline up to 30 days after last dose or to the beginning of the new anti-cancer therapy, up to 24 months
Incidence and severity of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Objective Response Rate (ORR)
时间窗: From baseline to first documented objective response, up to 24 months
Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator based on RECIST version 1.1.
次要结局
- Progression-free survival (PFS)(From baseline to the first documented disease progression or date of death (whichever occurs first), up to 24 months)
- Duration of response (DOR)(From the date of first objective response (CR or PR) to the date of first documentation of PD or death (whichever occurs first), up to 24 months)
- Disease control rate (DCR)(From baseline to date of first documented objective response (CR, PR, and SD), up to 24 months)
- Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of SKB264-ADC, SKB264-TAB and free KL610023(Cycle 1-8, every 4 cycles starting from Cycle 12 Day 1: pre-dose, post-dose (each cycle is 21 days), up to 24 months)
- Pharmacokinetic Parameter Minimum Plasma Concentration (Cmin) of SKB264-ADC, SKB264-TAB and free KL610023(Cycle 1-8, every 4 cycles starting from Cycle 12 Day 1: pre-dose, post-dose (each cycle is 21 days), up to 24 months)
- Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of KL-A167(Cycle 1-8, every 4 cycles starting from Cycle 12 Day 1: pre-dose, post-dose (each cycle is 21 days), up to 24 months)
- Pharmacokinetic Parameter Minimum Plasma Concentration (Cmin) of KL-A167(Cycle 1-8, every 4 cycles starting from Cycle 12 Day 1: pre-dose, post-dose (each cycle is 21 days), up to 24 months)
- Anti-drug Antibodies (ADA) for SKB264 and KL-A167(Cycle 1-8, every 4 cycles starting from Cycle 12 Day 1: pre-dose, post-dose (each cycle is 21 days), up to 24 months)