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

Обзор

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.

Вмешательства

• Препарат Limertinib+sintilimab+chemotherapy
  Experimental group 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.
• Препарат Limertinib+chemotherapy
  Control group group patients receive Limertinib for 6 weeks. Within 7 days thereafter, imaging assessment will be performed. If no progression is observed, control group patients receive Lilotinib for next 9 weeks + Carboplatin/Cisplatin + Pemetrexed every 3 weeks for 3 cycles.
• Процедура surgery
  The surgical procedure may involve minimally invasive surgery (video-assisted thoracoscopic surgery, robot-assisted surgery) or open thoracotomy. The surgical methods include lobectomy, combined lobectomy, pneumonectomy, sleeve resection, and ipsilateral systematic mediastinal lymph node dissection (for left-sided tumors, stations 4L, 5, 6, 7, and 9 should be included; for right-sided tumors, at least stations 2R, 3A, 4R, 7, and 9 should be included).
• Препарат Osimertinib
  Adjuvant treatment with Osimertinib for 2 years

Первичные конечные точки

• Pathologic Complete Response Rate [Срок оценки: Up to approximately 6 weeks following completion of surgery]

Вторичные конечные точки (6)

• Major Pathological Response (mPR) Rat [Срок оценки: Up to approximately 6 weeks following completion of surgery]
• Event Free Survival (EFS) [Срок оценки: Up to approximately 2.5 years following the beginning of Post-operative Assessment baseline]
• Disease free survival (DFS) [Срок оценки: Up to approximately 2 years following the begining of Post-operative Assessment baseline]
• Overall survival (OS) [Срок оценки: Up to approximately 2.5 years]
• Objective response rate(ORR) [Срок оценки: Up to approximately 2 weeks before surgery]
• Safety parameters:AE [Срок оценки: Up to approximately 2.5 years]

Критерии участия

Критерии включения

• 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 ≤1.
• Measurable lesions per RECIST v1.1.
• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 6 центров

• Affiliated Cancer Hospital and Institute of Guangzhou Medical Univercity — Гуанчжоу
• Guangdong Province People's Hospital — Гуанчжоу
• Sun Yet-Sen University Cancer Center — Гуанчжоу
• Hunan Cancer Hospital — Чанша
• Xiangya Hospital Central South University — Чанша
• The Second Affiliated Hospital Zhejiang University School of Medicine — Ханчжоу

Идентификаторы

NCT: NCT07038460 · GuangdongPPHosp

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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