Radiotherapy Plus Anti-PD-1 Versus Anti-PD-1 Alone in ypTanyN⁺M0 NSCLC

Официальное название

Postoperative Involved-field Nodal Radiotherapy Plus Anti-PD-1 Maintenance Versus Anti-PD-1 Maintenance Alone in Patients With ypTanyN⁺M0 NSCLC After Neoadjuvant Chemoimmunotherapy and R0 Resection: A Single-center Randomized Phase II Study

Обзор

Patients with stage III non-small-cell lung cancer (NSCLC) who receive neoadjuvant chemoimmunotherapy may achieve good response in the primary tumor but still have residual nodal disease after surgery (ypTanyN⁺M0), which is associated with poor prognosis in retrospective analyses from our center. In prior trials such as LungART and PORT-C, postoperative radiotherapy (PORT) did not improve disease-free survival in completely resected stage IIIA-N2 NSCLC after adjuvant chemotherapy, suggesting that PORT should not be used indiscriminately. However, recent preclinical and translational data indicate that radiotherapy can enhance antitumor immunity, remodel the tumor microenvironment, and synergize with immune checkpoint inhibitors via immunogenic cell death, improved T-cell trafficking, and tertiary lymphoid structure formation. This single-center randomized phase II study will evaluate whether adding postoperative involved-field nodal radiotherapy to standard PD-1 maintenance therapy can improve disease-free survival compared with PD-1 maintenance alone in patients with ypTanyN⁺M0 NSCLC after neoadjuvant chemoimmunotherapy and R0 resection.

Вмешательства

• Лучевая терапия radiotherapy
  Postoperative external beam radiotherapy to regional draining lymph nodes (e.g., ipsilateral mediastinal and hilar nodal stations involved or at high risk), based on pre-treatment imaging and surgical/pathologic findings. Suggested dose: 50-54 Gy in 25-27 fractions (2.0-2.16 Gy per fraction, once daily, 5 days per week), delivered with 3D-CRT or IMRT per institutional standards.
• Препарат PD -1/PD-L1 monoclonal antibody
  Anti-PD-1 monoclonal antibody administered intravenously every 3 weeks for up to 1 year (or until disease recurrence, unacceptable toxicity, or withdrawal). The specific agent and dose will follow the neoadjuvant regimen and local regulatory approval.

Первичные конечные точки

• Disease-Free Survival (DFS) [Срок оценки: 3 years]

Вторичные конечные точки (2)

• Overall Survival (OS) [Срок оценки: 5 years]
• Incidence of Treatment-Emergent Adverse Events [Срок оценки: Through treatment completion, an average of 1 year]

Критерии участия

Критерии включения

• Age 18-75 years, male or female.
• Histologically confirmed NSCLC (adenocarcinoma, squamous cell carcinoma, or other NSCLC subtypes).
• Clinical stage IIIA/IIIB at initial diagnosis, deemed suitable for neoadjuvant chemoimmunotherapy followed by surgery according to MDT.
• Completed 2-4 cycles of platinum-based doublet chemotherapy plus PD-1 inhibitor as neoadjuvant therapy.
• Underwent R0 resection (anatomical lobectomy or pneumonectomy with mediastinal lymph node dissection).
• Postoperative pathological stage ypT\_anyN⁺M0 (residual nodal metastasis in mediastinal or hilar lymph nodes).
• ECOG performance status 0-1.
• Adequate hematologic, hepatic, and renal function per protocol-defined lab thresholds.
• Able to start postoperative radiotherapy and/or PD-1 maintenance within 4-10 weeks after surgery (or after recovery from postoperative complications, as clinically appropriate).
• Signed written informed consent.

Критерии исключения

• Positive surgical margins (R1 or R2) or incomplete resection.
• Prior thoracic radiotherapy that would overlap with planned treatment fields.
• Active, uncontrolled infection or unresolved ≥ Grade 2 immune-related adverse events.
• History of severe autoimmune disease requiring systemic immunosuppression.
• Uncontrolled interstitial lung disease or significant pulmonary fibrosis.
• Symptomatic or untreated central nervous system metastases at enrollment.
• Any condition that, in the investigator's judgment, would compromise patient safety or protocol compliance.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07353476 · B2026GRI

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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