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

NCT07353476 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: B2026GRI
• Study Type: interventional
• Target: 38
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer); Post Surgical

Keywords

Radiotherapy; Adjuvant therapy; Lymph node

Outcome Measures

Primary Outcomes (1)

• Disease-Free Survival (DFS)

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

  3 years

Secondary Outcomes (2)

• Overall Survival (OS)

  5 years

• Incidence of Treatment-Emergent Adverse Events

  Through treatment completion, an average of 1 year

Study Arms (2)

Involved-field radiotherapy to regional draining lymph nodes + PD-1 maintenance

ACTIVE COMPARATOR

Radiation: radiotherapy; Drug: PD -1/PD-L1 monoclonal antibody

No radiotherapy (standard of care) + PD-1 maintenance

ACTIVE COMPARATOR

Drug: PD -1/PD-L1 monoclonal antibody

Interventions

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.

Involved-field radiotherapy to regional draining lymph nodes + PD-1 maintenance

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.

Involved-field radiotherapy to regional draining lymph nodes + PD-1 maintenance; No radiotherapy (standard of care) + PD-1 maintenance

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2026
• First Posted: January 20, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2032
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share