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

Overview

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.

Interventions

• Drug 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.
• Drug 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.
• Procedure 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).
• Drug Osimertinib
  Adjuvant treatment with Osimertinib for 2 years

Primary outcome measures

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

Secondary outcome measures (6)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 6 centers

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

Identifiers

NCT: NCT07038460 · GuangdongPPHosp

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗