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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
134
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.
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.
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).
Adjuvant treatment with Osimertinib for 2 years
Affiliated Cancer Hospital and Institute of Guangzhou Medical Univercity
Guangzhou, Guangdong, China
Guangdong Province People's Hospital
Guangzhou, Guangdong, China
Sun Yet-Sen University Cancer Center
Guangzhou, Guangdong, China
Hunan Cancer Hospital
Changsha, Hunan, China
Xiangya Hospital Central South University
Changsha, Hunan, China
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Pathologic Complete Response Rate
Pathology evaluation confirmed no residual tumor cells in the resected specimen and regional lymph nodes.
Time frame: Up to approximately 6 weeks following completion of surgery
Major Pathological Response (mPR) Rat
mPR rate is defined as ≤ 10% residual invasive viable tumor in both the primary tumor (lung) and the sampled lymph nodes after neoadjuvant therapy.
Time frame: Up to approximately 6 weeks following completion of surgery
Event Free Survival (EFS)
EFS is defined as the time from randomization to the first recorded time to any first documented progression, recurrence or death, which occurs first.
Time frame: Up to approximately 2.5 years following the beginning of Post-operative Assessment baseline
Disease free survival (DFS)
DFS is defined as the time from surgery to disease recurrence or death due to any cause.
Time frame: Up to approximately 2 years following the begining of Post-operative Assessment baseline
Overall survival (OS)
OS is defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 2.5 years
Objective response rate(ORR)
The proportion of patients in whom tumor volume reduction reached the predetermined criteria and was maintained for the minimum required duration is the sum of the complete response (CR) and partial response (PR) rates.
Time frame: Up to approximately 2 weeks before surgery
Safety parameters:AE
The relationship of study drug and the severity of all adverse events (AEs), treatment emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), immune-related adverse events (irAEs), serious adverse events (SAEs), infusion-related reactions (IRRs) and surgery delay rate.
Time frame: Up to approximately 2.5 years
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