A Randomized, Open-label, Phase Ib Clinical Study to Evaluate the Efficacy and Safety of IBI110 in Combination With Sintilimab Versus Sintilimab Alone in Neoadjuvant and Adjuvant Therapy of Radically Resectable Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Incidence of serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs)
研究概览
简要总结
The main purpose of this study is to evaluate the neoadjuvant therapy efficacy of IBI110 in combination with sintilimab versus sintilimab alone based on pathologic complete response (pCR) rate in stage IIB (primary tumor > 4 cm ) to IIIB (N2 only) subjects with radically resectable 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
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
- •Have NSCLC that has been classified as stage IIB (primary tumor > 4 cm), IIIA, or IIIB (N2 only) per the 8th edition of TNM staging system of International Association for the Study of Lung Cancer (IASLC) and the American Joint Committee on Cancer (AJCC).
- •Subjects with non-squamous NSCLC should undergo genetic testing to confirm the absence of epidermal growth factor receptor (EGFR) sensitizing mutations or anaplastic lymphoma kinase (ALK) rearrangements;
- •Eligible for radical resection (R0 resection) at the thoracic surgeon's discretion, and the lung function meets the criteria for planned surgery;
- •Have at least one measurable lesion per RECIST v1.1 criteria;
- •Have a performance scale of 0 or 1 on the Eastern Cooperative Oncology Group Performance Status (ECOG PS)
排除标准
- •Have pathological evidence for small cell carcinoma, neuroendocrine carcinoma, sarcoma, lymphoepithelial rumen carcinoma, salivary gland tumor, or mesenchymal tumor from the biopsy.
- •Have been previously exposed to immune-mediated therapies, including but not limited to LAG-3 antibody drugs, anti-cytotoxic T lymphocyte antigen-4 (CTLA-4), anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies.
研究组 & 干预措施
IBI110+sintilimab
IBI110 and sintilimab will be administered as intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks) for 3 cycles during the neoadjuvant treatment phase. IBI110 and sintilimab will be administered as IV infusion 3 weeks during the post-operative adjuvant phase up to 1 year.
干预措施: IBI110 (Drug)
IBI110+sintilimab
IBI110 and sintilimab will be administered as intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks) for 3 cycles during the neoadjuvant treatment phase. IBI110 and sintilimab will be administered as IV infusion 3 weeks during the post-operative adjuvant phase up to 1 year.
干预措施: sintilimab (Drug)
sintilimab
Sintilimab will be administered as intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks) for 3 cycles during the neoadjuvant treatment phase. Sintilimab will be administered as IV infusion 3 weeks during the post-operative adjuvant phase up to 1 year.
干预措施: sintilimab (Drug)
结局指标
主要结局
Incidence of serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs)
时间窗: up to 90 days after the last administration
An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is an important medical event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed before. A TEAE will be defined as any new AE that begins, or any pre-existing condition that worsens in severity, after at least 1 dose of study treatment has been administered. irAEs will be assessed.
pCR
时间窗: Approximately 21 to 28 days after operation
defined as having no residual visible tumor cells in the surgically resected primary tumor and lymph node samples (ypT0N0)
Number of participants with abnormality in vital signs
时间窗: up to 90 days after the last administration
Blood pressure, pulse, respiratory rate, and temperature will be assessed.
Number of participants with abnormality in hematology parameters
时间窗: up to 90 days after the last administration
Blood samples will be collected to evaluate hemoglobin, mean corpuscular volume (MCV), white blood cell (WBC) count, platelets, 5-part differential white cell count, mean platelet volume and coagulation factors including international normalized ratio (INR), activated partial thromboplastin time (aPTT) and prothrombin time (PT).
Number of participants with abnormality in clinical chemistry parameters
时间窗: up to 90 days after the last administration
Blood samples will be collected to evaluate sodium, potassium, calcium, magnesium, chloride, glucose, creatinine, urea or BUN, bicarbonate, amylase, bilirubin, alkaline phosphatase, AST, ALT, total protein, albumin, lactate dehydrogenase and lipase.
Number of participants with abnormality in routine urinalysis parameters
时间窗: up to 90 days after the last administration
Urine samples will be collected to evaluate specific gravity, leucocyte esterase, nitrite, blood, bilirubin, protein, glucose, ketones and urobilinogen.
Number of participants with abnormality in ECG parameters
时间窗: up to 90 days after the last administration
12-lead ECG will be obtained using an ECG machine. Participants will be in supine or a semi-recumbent position (about 30 degrees of elevation) and rested for approximately 2 minutes before ECGs are recorded.
次要结局
- major pathological response (MPR) rate(Approximately 21 to 28 days after operation)
- radical resection (R0 resection) rate(Approximately 21 to 28 days after operation)
- ORR （Objective Response rate,）(Within 7 days before surgery)
- OS （Overall Survival）(up to 3 years)
- Immunogenicity(From date of randomization to 30 days after last dose of the drug)
- EFS （Event Free Survival）(up to 3 years)
- maximum concentrations (Cmax )(from first administration of IBI110 to 3 days before the operation)
- the area under the drug plasma concentration-time curve (AUC)(from first administration of IBI110 to 3 days before the operation)
- half-life (t1/2)(from first administration of IBI110 to 3 days before the operation)
- clearance (CL)(from first administration of IBI110 to 3 days before the operation)
- volume of distribution (V).(from first administration of IBI110 to 3 days before the operation)