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This is a prospective, open, multicenter, Phase II single-arm clinical study. In subjects with an initial stage of stage III-N3 non-small cell lung cancer (NSCLC) that was negative for sensitive gene mutations and had not received any systemic or local therapy (T1-4N3M0, excluding primary tumor or metastatic lymph node invasion of the aorta/trachea/esophagus/heart, etc.); After 3-4 cycles of Tislelizumab combined with platinum-containing dual agents, the patients without disease progression were evaluated by MDT and selected according to the patient's wishes, including those who could receive conventional/standard radical lung cancer surgery (excluding total lung resection). Conventional/standard resection of primary, ipsilateral hilum and ipsilateral mediastinum combined with hypofractionted chemoradiotherapy of N3 metastatic lymph nodes was performed. For patients who are inoperable or unwilling to undergo surgery or intolerant to surgery, conventional concurrent chemoradiotherapy is given. Maintenance therapy with Tislelizumab was continued after local treatment until disease progression, drug intolerance as assessed by imaging, or after 1 year; Participants were followed up according to the procedure to evaluate efficacy and patient-reported outcomes.
The study included a screening period (no more than 28 days after subjects signed informed consent to the first dose), a treatment period (including Tislelizumab combined with chemotherapy-restaging and MDT-local treatment-maintenance therapy), and a follow-up period.
Thirty patients:30 patients Primary endpoint: 1-year EFS rate Secondary endpoints: EFS, OS, surgical rate, TTDM, TTLR, AEs, PROs Exploratory end points: Imaging efficacy, pathological efficacy and other relevant clinical outcomes; Predictive biomarkers based on tissue and blood samples.
This is a prospective, multicenter, single arm phase 2 clinical trial enrolling 30 newly diagnosed stage III NSCLC patients with N3 lymph-node metastasis (T1-4N3M0, AJCC 9th edition). Mainly eligible patients must be negative for sensitive gene muta-tions, treatment-naive for systemic or local therapy, aged ≥18 years, and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with at least one measurable lesion according to RECIST 1.1 criteria at baseline. Key exclu-sion criteria include invasion of critical structures such as the aorta, trachea, esopha-gus, or heart by the primary tumor or metastatic lymph nodes, as well as the presence of Pancoast tumors. Following induction therapy with 3-4 cycles of Tislelizumab combined with platinum-based chemotherapy, patients without disease progression will be evaluated by a multidisciplinary team (MDT) and assigned to treatment strategies based on eligibility and patient preference. Patients deemed eligible to surgery will receive standard lung cancer resection (excluding total pneumonectomy), including removal of the primary tumor, ipsilateral hilar, and ipsilateral mediastinal lymph nodes, followed by hypofractionated chemoradiotherapy targeting N3 meta-static lymph nodes. Patients ineligible for or unwilling to undergo surgery will re-ceive definitive conventional CRT. After completion of local treatment, all patients will continue Tislelizumab maintenance therapy until radiographic disease progres-sion, unacceptable toxicity, or completion of one year of treatment. The primary endpoint is the 1-year event-free survival rate (1y-EFS rate). Secondary endpoints include EFS, overall survival (OS), surgical conversion rate, time to distant metasta-sis (TTDM), time to local recurrence (TTLR), adverse events (AEs), and the impact of the integrated treatment approach on patient-reported outcomes (PROs). Explora-tory analyses will be conducted to identify predictive and prognostic biomarkers us-ing tumor tissue and blood samples collected at multiple time points during the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tislelizumab + Chemotherapy +Local Treatments (Surgery and Radiotherapy or Radiotherapy Alone) | Experimental | Following induction therapy with 3-4 cycles of Tislelizumab combined with platinum-based chemotherapy, patients without disease progression will be evaluated by a multidisciplinary team (MDT) and assigned to treatment strategies based on eligibility and patient preference. Patients deemed eligible to surgery will receive standard lung cancer resection (excluding total pneumonectomy), including removal of the primary tumor, ipsilateral hilar, and ipsilateral mediastinal lymph nodes, followed by hypofractionated chemoradiotherapy targeting N3 metastatic lymph nodes. Patients ineligible for or unwilling to undergo surgery will receive definitive conventional CRT. After completion of local treatment, all patients will continue Tislelizumab maintenance therapy until radiographic disease progression, unacceptable toxicity, or completion of one year of treatment. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 3-4 cycles of Tislelizumab combined with platinum-based chemotherapy, evaluated by MDT and assigned to treatment strategies based on eligibility and patient preference. | Drug | Patients deemed eligible to surgery will receive standard lung cancer resection (excluding total pneumonectomy) |
| Measure | Description | Time Frame |
|---|---|---|
| 1-year EFS rate | The 1-year Event-Free Survival (EFS) rate is defined as the proportion of patients who have not experienced an EFS event at one year after the first administration of the study drug. EFS is defined as the time from the first dose of the study treatment until the first objective documentation of disease progression that renders the patient unresectable or ineligible for curative radiotherapy, local recurrence, distant metastasis, or death from any cause, whichever occurs first. EFS is assessed by the investigator based on RECIST v1.1 criteria using the curative intent treatment analysis set. | treatment period:Induction therapy (Day 1 of medication); Surgery+Radiotherapy/Radiotherapy; maintenance therapy (one year). follow-up period:One year after the completion of maintenance therapy (one year). |
| Measure | Description | Time Frame |
|---|---|---|
| Secondary endpoints: EFS, OS, surgical rate, TTDM, TTLR, AEs, PROs | OS: The duration from study enrollment to death from any cause. Surgical rate: Percentage of operable patients receiving surgical resection. TTDM: The percentage of patients from enrollment to the first detection of tumor metastasis in distant organs or tissues compared to the number of patients in the corresponding treatment group. TTLR: The percentage of patients with tumor recurrence at the primary lesion or adjacent area after treatment compared to the number of patients in the corresponding treatment group. AEs: Classify and grade adverse events according to the latest version of the Common Terminology Criteria for Adverse Events (CTCAE), and assess the incidence, severity, and causal relationship of treatment-related adverse events. PROs: Collect data directly from patients regarding their health status or treatment impact using specific tools (such as FACT-G), without interpretation by healthcare professionals, to provide a patient perspective on treatment effects. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ailin Li | Contact | +86 18509860482 | liailin0312@163.com |
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| treatment period:Induction therapy (Day 1 of medication); Surgery+Radiotherapy/Radiotherapy; maintenance therapy (one year). follow-up period:One year after the completion of maintenance therapy (one year). |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D017671 | Platinum Compounds |
| ID | Term |
|---|---|
| D007287 | Inorganic Chemicals |
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