A Multicenter Phase II Randomized Trial of Limertinib Followed by Sintilimab and Chemotherapy vs. Limertinib Followed by Limertinib and Chemotherapy as Neoadjuvant Therapy in Resectable Stage II-IIIB EGFR-Mutant NSCLC
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 134
- 试验地点
- 6
- 主要终点
- Pathologic Complete Response Rate
研究概览
简要总结
This clinical trial aims to evaluate the efficacy and safety of neoadjuvant therapy with Limertinib Followed by Sintilimab and Chemotherapy in resectable Stage II-IIIB EGFR-Mutant NSCLC. Untreated stage II-IIIB NSCLC (AJCC 8th edition) patients assessed as surgically resectable by investigators will be randomized 1:1 into the experimental or control group after signing informed consent and meeting eligibility criteria. All patients receive Limertinib for 6 weeks. Within 7 days thereafter, imaging assessment will be performed. If no progression is observed, experimental group patients discontinue therapy for 1 week, then receive Sintilimab + Carboplatin/Cisplatin + Pemetrexed every 3 weeks for 3 cycles; control group patients receive Limertinib for 9 weeks and Carboplatin/Cisplatin + Pemetrexed every 3 weeks for 3 cycles. Preoperative tumor assessment is required. Surgery will be performed 2-6 weeks (±7 days) after the first dose of the final cycle. Then patients will recieve 2-year adjuvant Osimertinib starting 1 month post-surgery. If imaging assessment after 6 weeks of limertinib treatment shows lesion enlargement but remains confined to stage II-IIIB, the investigator will decide whether the patient continues study treatment or not; if progression occurs to unresectable stage III or advanced disease, the patient must discontinue. The primary endpoint is pathological complete response (pCR) rate.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent form
- •Age: 18-75 years.
- •Cytologically/histologically confirmed (via percutaneous lung puncture, bronchoscopy, mediastinoscopy, etc.), previously untreated stage II-IIIB (IASLC 8th Edition Thoracic Tumor Classification) lung adenocarcinoma.
- •Tumor tissue or blood samples confirmed as EGFR-sensitive or rare mutation-positive by laboratory testing
- •Must provide archived tumor tissue or newly resected tumor biopsy samples for PD-L1 IHC testing during screening.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Measurable lesions per RECIST v1.
- •Surgically evaluated as eligible for local surgical resection (adequate pulmonary/organ function).Surgically evaluated as eligible for local surgical resection (adequate pulmonary/organ function).
- •Adequate organ and bone marrow function (within 7 days prior to enrollment; no corrective therapies within 14 days prior to testing): • Hematology: ANC ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥100 g/L. • Hepatic: Total bilirubin ≤1.5×ULN; AST/ALT ≤2.5×ULN; albumin ≥35 g/L. • Renal: Serum creatinine ≤1.5×ULN; CrCl ≥60 mL/min (Cockcroft-Gault formula); urine protein <2+ or 24-hour urine protein <1 g. Cockcroft-Gault formula: • Female: CrCl = [(140 - age) × weight (kg) × 0.85] / [72 × serum creatinine (mg/dL)]. • Male: CrCl = [(140 - age) × weight (kg)] / [72 × serum creatinine (mg/dL)]. • Coagulation: INR ≤1.5×ULN; PT/APTT ≤1.5×ULN.
- •For women of childbearing potential: Negative urine/serum pregnancy test within 7 days prior to first dose. Confirmatory blood test required if urine test is positive.
排除标准
- •Patients with stage I or IV NSCLC who have previously received systemic anti-tumor therapies (e.g., ICIs, targeted therapy, chemotherapy).
- •Active known or suspected autoimmune diseases (exceptions: type I diabetes, hypothyroidism requiring hormone replacement only, non-progressive skin conditions like vitiligo/psoriasis/alopecia).
- •Active hepatitis B (HBsAg-positive) or hepatitis C (HCV RNA-positive). Patients with resolved HBV infection (HBsAg-negative, HBcAb-positive) must provide HBV DNA-negative results. HCV antibody-positive patients require negative HCV RNA PCR.
- •HIV-positive or AIDS history.
- •Arterial thrombosis within 6 months, or deep vein thrombosis/pulmonary embolism within 3 months.
- •Uncontrolled angina, arrhythmias, or congestive heart failure.
- •Active malignancies within 5 years (except cured cervical/cutaneous carcinoma in situ, superficial bladder/prostate/breast cancer).
- •Contraindications to local therapies (surgery, radiotherapy, or intervention) per investigator judgment.
- •Hypersensitivity to sintilimab, limertinib, chemotherapy agents, or excipients.
- •Unwillingness to sign informed consent or comply with follow-up.
- •Any condition compromising trial integrity or patient safety, as judged by the investigator.
研究组 & 干预措施
Experimental Group
干预措施: Limertinib+sintilimab+chemotherapy (Drug)
Experimental Group
干预措施: surgery (Procedure)
Experimental Group
干预措施: Osimertinib (Drug)
Control Group
干预措施: Limertinib+chemotherapy (Drug)
Control Group
干预措施: surgery (Procedure)
Control Group
干预措施: Osimertinib (Drug)
结局指标
主要结局
Pathologic Complete Response Rate
时间窗: Up to approximately 6 weeks following completion of surgery
Pathology evaluation confirmed no residual tumor cells in the resected specimen and regional lymph nodes.
次要结局
- Overall survival (OS)(Up to approximately 2.5 years)
- Major Pathological Response (mPR) Rat(Up to approximately 6 weeks following completion of surgery)
- Event Free Survival (EFS)(Up to approximately 2.5 years following the beginning of Post-operative Assessment baseline)
- Disease free survival (DFS)(Up to approximately 2 years following the begining of Post-operative Assessment baseline)
- Objective response rate(ORR)(Up to approximately 2 weeks before surgery)
- Safety parameters:AE(Up to approximately 2.5 years)
研究者
Wen-zhao ZHONG
Ph.D
Guangdong Provincial People's Hospital