Neoadjuvant Nivolumab Plus Ipilimumab in Resectable Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- Pathological Complete Response (PCR)
研究概览
简要总结
Neoadjuvant immunotherapy followed by surgery has emerged as the standard treatment for locally advanced and resectable non-small cell lung cancer (NSCLC). However, conventional chemotherapy components may increase treatment-related toxicity, particularly in elderly populations. Additionally, the efficacy of preoperative immunochemotherapy for patients with PD-L1 expression <1% remains to be improved. Emerging evidence has demonstrated that the combination of nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) provides superior responses in the treatment of advanced NSCLC. However, the safety and efficacy of this strategy in the neoadjuvant setting remain controversial. Therefore, this single-arm clinical trial aims to evaluate the safety and feasibility of neoadjuvant nivolumab plus ipilimumab followed by surgery in treating locally advanced and resectable NSCLC.
详细描述
Lung cancer remains the leading cause of cancer-related death globally. Neoadjuvant immunotherapy followed by surgery has been emerged as the standard treatment for locally advanced and resectable non-small cell lung cancer (NSCLC). Numerous clinical trials highlighted the efficacy of preoperative immunochemotherapy, including remarkably shrinking the primary lesion, eliminating micrometastases and ultimately contributing to survival outcomes. Notably, studies also demonstrated neoadjuvant immunochemotherapy increased the access of modified surgery and enhanced survival prognosis of patients with locally advanced NSCLC (IIIB).
Despite these advances, certain limitations remain. Conventional chemotherapy components may elevate treatment-related toxicity, particularly in elderly populations. Additionally, the efficacy of preoperative immunochemotherapy for patients with PD-L1<1% remained to be improve. Emerging evidences demonstrated that nivolumab (anti-PD-1) combine with ipilimumab (antiCTLA-4) provided superior response for the treatment of advanced NSCLC patients. However, the safety and efficacy of this strategy in the neoadjuvant setting remain controversial. Therefore, this single-arm clinical trial aims to evaluate the safety and feasibility of neoadjuvant nivolumab plus ipilimumab followed by surgery in treating locally advanced and resectable NSCLC. The study will enroll 69 eligible participants, with the primary endpoint being pathological complete response (pCR) rate following neoadjuvant therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed consent must be signed.
- •At least 18 years of age.
- •Histologically or cytologically confirmed non-small cell lung cancer (without EGFR, ALK mutation).
- •Have measurable and clinical stage II-IIIA with no known PD-L1 expression or PD-L1 ≤ 1%.
- •disease eligible for surgery.
- •No previous systematic therapy or radiotherapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •At least one measurable lesion.
- •No major organ dysfunction, including liver, kidney, and cardiac function.
排除标准
- •Patients with active autoimmune disease or history of autoimmune disease.
- •Patients have received other treatment for non-small cell lung cancer or for any other malignancy.
- •History of allergy to study drug components.
- •Pregnant or breast-feeding.
- •Any mental or psychological condition that would prevent the patient from completing the study or understanding the patient information.
- •Patients who have other malignancies.
- •History of major surgery or serious injury within the past 3 months.
- •HIV, HBV, HCV infection or active pulmonary tuberculosis.
- •Vaccination within 4 weeks prior to the start of the study.
- •Presence of underlying medical conditions that, in the investigator's judgment, could increase the risk associated with study drug administration or interfere with the assessment of toxicity and adverse events.
研究组 & 干预措施
Neoadjuvant treatment
Patients with IIA-IIIB NSCLC will received 2-3 cycles of neoadjuvant Nivolumab (3 mg/kg intravenously (i.v.), every 3 week) plus Ipilimumab (1 mg/kg i.v., every 6 week).
Surgery will be performed within 4 to 6 weeks after completion of preoperative therapy.
After the second cycles treatment, contrast-enhanced chest CT will be performed to evaluate the tumor.
干预措施: Nivolumab & Ipilimumab (Drug)
结局指标
主要结局
Pathological Complete Response (PCR)
时间窗: Within 2 weeks after surgery
Pathological complete response is predefined as no residual viable tumor cells in primary tumor and lymph nodes.
次要结局
- 3-year Event-Free Survival (3-year EFS）(From neoadjuvant treatment to the date of death, recurrence, progression, or the last follow-up (assessed up to 3 years).)
- Major Pathological Response (MPR)(Within 2 weeks after surgery)
- Safety (Rate of grade 3 and higher grade treatment-related adverse events (TRAEs))(Between the last dose of neoadjuvant treatment and surgery (assessed up to 30 days))
- Radiological Response(Between the last dose of neoadjuvant treatment and surgery)
- Postoperative complications(After the surgery assess to 90 days)
- Intraoperative bleeding(Up to approximately 20 weeks)
- The Quality of Life(From the Day 1 to at least 90 days after surgery)
- Duration of surgery(Up to approximately 20 weeks)
- Hospital Stay(Up to approximately 20 weeks)
- Feasibility (Completion rate of neoadjuvant treatment and surgery)(From date of treatment allocation until surgery, assessed up to 5 months)
研究者
Shuben Li
Director, Training Program of Thoracic Surgery, Director, Section of Tracheal and Pulmonary Surgery, Thoracic Surgery Department
The First Affiliated Hospital of Guangzhou Medical University