NCT06908733

Integrating Surgery and Radiotherapy Following Tislelizumab-based Conversion Therapy in N3-Stage III NSCLC

Prognosis and Patient-Reported Outcomes of Combined Local Treatments (Surgery and Radiotherapy or Radiotherapy Alone) With Tislelizumab and Chemotherapy in Initial Stage III-N3 Non-Small Cell Lung Cancer: A Prospective, Open-Label, Single-Arm, Phase II Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Liaoning Cancer Hospital & Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Non-Small Cell Lung Cancer (Stage III)

Interventions

Type	Name	Description
DRUG	3-4 cycles of Tislelizumab combined with platinum-based chemotherapy, evaluated by 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)

Timeline

• Start date: 2025-03-31
• Primary completion: 2027-09-30
• Completion: 2029-12-30
• First posted: 2025-04-03
• Last updated: 2025-04-03

Regulatory

• FDA-regulated drug study