Multimodal Ablation Combined With Perioperative Tislelizumab and Chemotherapy for Resectable II-IIIB NSCLC

Обзор

This is a prospective, open-label, single-center, single-arm phase II clinical trial evaluating the efficacy and safety of multimodal ablation in combination with perioperative tislelizumab and chemotherapy in patients with pathologically confirmed resectable stage II-IIIB (N2) non-small cell lung cancer (NSCLC).

Подробное описание

Eligible patients will receive multimodal ablation, followed by perioperative tislelizumab in combination with platinum-based doublet chemotherapy, and subsequently undergo radical surgical resection. Adjuvant tislelizumab will be continued after surgery.The primary endpoint is the pathological complete response (pCR) rate. Secondary endpoints include major pathological response (MPR) rate, event-free survival (EFS), overall survival (OS), and safety.

Вмешательства

• Устройство Multimodal Ablation
  CT-guided preoperative multimodal ablation performed with multimodal tumor therapy system.Target lung lesions are ablated within 2 weeks after subject enrollment.
• Препарат Neoadjuvant therapy
  Neoadjuvant tislelizumab (200 mg, IV, Q3W) combined with chemotherapy will be administered within 2 weeks after ablation. For patients with squamous NSCLC, cisplatin or carboplatin combined with paclitaxel will be used; for patients with non-squamous NSCLC, cisplatin or carboplatin combined with pemetrexed will be used, for a total of 3-4 cycles of treatment.
• Процедура Surgery
  Surgical resection will be performed within 4-6 weeks after the last neoadjuvant treatment. The pulmonary lesions (including the ablated lesions) will be radically resected via surgery.
• Препарат Adjunctive therapy
  Adjuvant therapy will be initiated within 2-8 weeks after surgery. Postoperative adjuvant therapy with tislelizumab (400 mg, Q6W) will be maintained for up to 1 year. Concomitant chemotherapy is allowed during this period based on guidelines/consensus or multidisciplinary team (MDT) discussion.

Первичные конечные точки

• Pathological Complete Response Rate [Срок оценки: Perioperative]

Вторичные конечные точки (4)

• Major Pathological Response Rate [Срок оценки: Perioperative]
• Event-Free Survival [Срок оценки: Through study completion, up to 5 years]
• Overall Survival [Срок оценки: Through study completion, up to 5 years]
• Incidence and Severity of Adverse Events and Serious Adverse Events [Срок оценки: Through study completion]

Критерии участия

Критерии включения

• Age >= 18 years, either gender;
• Pathologically confirmed stage II-IIIB (N2) squamous or non-squamous non-small cell lung cancer (NSCLC) according to the 9th edition of the AJCC/UICC NSCLC staging system;
• Presence of lesions suitable for ablation therapy confirmed by imaging evaluation;
• Evaluated as resectable with R0 resection before enrollment, and consent to undergo radical surgical resection;
• ECOG performance status score of 0-1;
• Eligible for platinum-based doublet chemotherapy;
• Adequate cardiopulmonary function to meet the requirements of curative surgical resection;
• Sufficient organ function confirmed by laboratory tests within 28 days before enrollment:

• Blood routine: WBC >= 3.0×10\^9/L; ANC >= 1.5×10\^9/L; PLT >= 100×10\^9/L; HGB >= 90 g/L.
• Liver function: AST <= 5.0×ULN; ALT <= 5.0×ULN; TBIL <= 1.5×ULN;
• Renal function: Cr <= 1.5×ULN;
• For patients receiving cisplatin: creatinine clearance >= 60 mL/min.
• For patients receiving carboplatin: creatinine clearance >= 45 mL/min.
• Coagulation function: INR <= 1.5×ULN (<=3×ULN for patients on anticoagulants; anticoagulants must be discontinued for one week before ablation); APTT <= 1.5×ULN;
• Fully understand the study and voluntarily sign the informed consent form (ICF).

Критерии исключения

• Tumor is adjacent to the hilum, invades major blood vessels, or has contraindications for surgery;
• History of interstitial lung disease, non-infectious pneumonia, or uncontrolled pulmonary diseases including pulmonary fibrosis and acute lung disease;
• Previous allogeneic stem cell transplantation or organ transplantation;
• Previous radiotherapy or chemotherapy;
• Previous local treatment (e.g., radioactive seed implantation, ablation) for the target ablation lesion;
• Previous treatment with immune checkpoint inhibitors, including but not limited to anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies;
• Complicated with severe cardiac, pulmonary, hepatic, renal insufficiency, or coagulation disorders;
• Clinically significant cardio-cerebrovascular diseases, including but not limited to acute myocardial infarction within 6 months before enrollment, heart failure of NYHA class III or IV, ventricular arrhythmia ≥ grade 2, any history of cerebrovascular accident;
• Underwent any major surgical procedure requiring general anesthesia within 28 days before enrollment;
• Previous severe immune system diseases or active infection;
• Pregnant or lactating female;
• Complicated with other malignancies (un cured within 5 years);
• Confirmed positive EGFR or ALK driver genes by genetic testing;
• Any condition requiring systemic therapy with corticosteroids (>10 mg prednisone per day or equivalent) or other immunosuppressive drugs before enrollment;
• Severe chronic or active infection requiring systemic antibacterial, antifungal, or antiviral therapy, including tuberculosis;
• Known history of HIV infection;
• Untreated chronic hepatitis B patients, chronic hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL, or active hepatitis C virus (HCV) patients; (Note: Inactive hepatitis B surface antigen carriers, treated and stable hepatitis B patients (HBV DNA < 500 IU/mL), and cured hepatitis C patients are eligible.);
• Received live vaccine within 28 days before enrollment;
• Simultaneously participating in another therapeutic clinical study;
• Other conditions considered unsuitable for participation in this study by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07729670 · NCP1-1111

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗