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

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.

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Key information

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer) Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Post Surgical Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

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.

Treatment and study plan

Radiotherapy

Radiation

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.

PD -1/PD-L1 monoclonal antibody

Drug

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.

Primary outcomes

Disease-Free Survival (DFS)

Time frame: 3 years

Time from date of surgery to first documented recurrence (locoregional or distant) or death from any cause, whichever occurs first.

Secondary outcomes

Overall Survival (OS)

Time frame: 5 years

Time from surgery to death from any cause (up to 5 years).
Incidence of Treatment-Emergent Adverse Events

Time frame: Through treatment completion, an average of 1 year

Incidence, type, and severity of adverse events graded by CTCAE v5.0, including radiation pneumonitis and immune-related toxicities.

Sponsors and collaborators

Lead sponsor

Shanghai Zhongshan Hospital

Other

Registry information

Official study title

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

Important dates

Study start: 2026
Primary completion: 2030
Study completion: 2032
First posted: Jan 20, 2026
Registry last updated: Jan 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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