Neoadjuvant Toripalimab Plus Chemotherapy for Resectable Stage II-IIIB Non-squamous Non-small Cell Lung Cancer With EGFR Mutation: a Multicentre, Multi-cohort, Exploratory Study.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 126
- 主要终点
- Pathologic Complete Response (pCR) Rate
研究概览
简要总结
This study was designed to investigate the efficacy and safety of neoadjuvant Toripalimab (anti-PD1) plus chemotherapy for patients with resectable II-IIIB non-squamous NSCLC harboring EGFR mutation, and to explore the potential predictive and prognostic biomarkers, aiming to provide more abundant evidences for the preoperative treatment decision of non-squamous NSCLC patients.
详细描述
Previous studies have confirmed the efficacy of neoadjuvant immunotherapy in NSCLC patients without driver gene mutation, while its efficacy in driver gene mutated patients is still controversial. This study was designed to investigate the efficacy and safety of neoadjuvant Toripalimab (anti-PD1) plus chemotherapy for patients with resectable II-IIIB non-squamous NSCLC harboring EGFR mutation, and to explore the potential predictive and prognostic biomarkers, aiming to provide more abundant evidences for the preoperative treatment decision of non-squamous NSCLC patients.
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
- 17 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of signed informed consent by the patient or legally acceptable representative;
- •Previously untreated, histologically confirmed resectable stage II-IIIA, IIIB(N2) (AJCC staging 8th edition) non-squamous non-small cell lung cancer;
- •Adequate tissue samples for PD-L1 immunohistochemical testing and gene mutations test by RT-pCR or NGS, or consent for blood RT-PCR or NGS if tissue samples are insufficient;
- •Harboring EGFR mutation (19del or L858R);
- •Aged 18-70 years, regardless of gender;
- •Eastern Cooperative Group (ECOG) Performance Status 0-1;
- •Acceptable cardiac function with a left ventricular ejection fraction >50%;
- •Acceptable respiratory function (FEV1>1.5L, DLCO>50%) and ability to tolerate radical lung cancer surgery;
- •Acceptable bone marrow haematopoiesis with leucocytes ≥ 4 x 10^9/L, neutrophils ≥ 1.5 x 10^9/L, haemoglobin ≥ 10g/dL and platelets ≥ 100 x 10^9/L;
- •Acceptable renal function with a glomerular filtration rate ≥ 60 mL/min;
- •Acceptable liver function with total bilirubin ≤ 1.5 x ULN, AST ≤ 3 x ULN, and ALT ≤ 3 x ULN;
- •Presence of measurable lesions as defined by RECIST 1.1 criteria;
- •Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 3 days prior to the start of study treatment, and agree to use effective contraception for the duration of study drug use and for 120 days after the last dose. Women of childbearing potential were defined as sexually mature females who 1) had not undergone hysterectomy or bilateral oophorectomy and 2) had not experienced spontaneous menopause for 12 consecutive months (amenorrhea after cancer treatment did not preclude fertility) (menstruation had occurred at any time during the previous 12 consecutive months).
排除标准
- •Pathological histologically confirmed small cell lung cancer, squamous epithelial cell carcinoma and other pathological subtypes cannot be enrolled;
- •Patients with advanced or metastatic lung cancer, or unresectable lung cancer, or who have received previous systemic anti-tumour therapy such as immunotherapy, chemotherapy or targeted therapy cannot be enrolled;
- •Patients with a history of active autoimmune disease or autoimmune disease that is likely to recur cannot be enrolled;
- •Patients with active hepatitis B and C requiring relevant antiviral therapy need to have HBV-DNA <500 IU/ml and have been on anti-HBV treatment for at least 14 days prior to study entry and continue treatment during the treatment period; HCV RNA-positive patients should be excluded;
- •Patients who are allergic to chemotherapeutic agents such as carboplatin, paclitaxel, albumin paclitaxel, pemetrexed;
- •Patients with a history of allergy to monoclonal antibody drugs;
- •Patients who have previously received an allogeneic stem cell transplant or organ transplant；
- •Patients with mental illness or any other illness that makes it impossible to comply with treatment；
- •Patients who are unable or unwilling to sign the informed consent form；
- •Patients with comorbidities or other conditions that, in the opinion of the investigator, may affect compliance with the protocol or make them unsuitable for participation in this study.
研究组 & 干预措施
19DEL cohort
Patients who participated in the trial with EGFR 19DEL mutation will be included in this arm.
干预措施: Toripalimab plus Chemotherapy (Drug)
L858R cohort
Patients who participated in the trial with EGFR L858R mutation will be included in this arm
干预措施: Toripalimab plus Chemotherapy (Drug)
结局指标
主要结局
Pathologic Complete Response (pCR) Rate
时间窗: Within 1 week after surgery
Pathologic complete response (pCR) rate is defined as the percentage of participants with no residual viable tumor in lung primary or lymph nodes as evaluated by blinded independent pathological review (BIPR).
次要结局
- Major Pathologic Response (MPR) Rate(Within 1 week after surgery)
- Event-free Survival (EFS)(Up to 24 months after participation)
- Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different EGFR mutations status(Within 1 week after surgery)
- Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different EGFR mutations status(Within 1 week after surgery)
- The Safety and Tolerability(Up to 24 months after participation)
- Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different PD-L1 expression levels(Within 1 week after surgery)
- Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different PD-L1 expression levels(Within 1 week after surgery)
研究者
Yang Fan, MD
Professor of Thoracic Surgery
Peking University People's Hospital