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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental Group | Experimental |
| |
| Control Group | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Limertinib+sintilimab+chemotherapy | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Pathologic Complete Response Rate | Pathology evaluation confirmed no residual tumor cells in the resected specimen and regional lymph nodes. | Up to approximately 6 weeks following completion of surgery |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to approximately 6 weeks following completion of surgery |
| Event Free Survival (EFS) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jin Kang | Contact | 020 8382 7812 | kangjin@gdph.org.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Affiliated Cancer Hospital and Institute of Guangzhou Medical Univercity | Guangzhou | Guangdong | China |
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| Limertinib+chemotherapy | Drug | 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. |
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| surgery | Procedure | 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). |
|
| Osimertinib | Drug | Adjuvant treatment with Osimertinib for 2 years |
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EFS is defined as the time from randomization to the first recorded time to any first documented progression, recurrence or death, which occurs first. |
| 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. | 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. | 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. | 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. | Up to approximately 2.5 years |
| Guangdong Province People's Hospital | Guangzhou | Guangdong | China |
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| Sun Yet-Sen University Cancer Center | Guangzhou | Guangdong | China |
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| Hunan Cancer Hospital | Changsha | Hunan | China |
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| Xiangya Hospital Central South University | Changsha | Hunan | China |
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| The Second Affiliated Hospital Zhejiang University School of Medicine | Hangzhou | Zhejiang | China |
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| ID | Term |
|---|---|
| D013514 | Surgical Procedures, Operative |
| C000596361 | osimertinib |
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