Neoadjuvant SBRT Followed by Sintilimab Plus Chemotherapy for N3-Positive NSCLC

NCT07309952 | Recruiting Phase 2 DMC

• 1 other identifier: B2025-696-01
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II clinical trial evaluating the efficacy and safety of a new treatment approach for patients with locally advanced non-small cell lung cancer (NSCLC) that has spread to lymph nodes on the opposite side of the chest (known as N3 lymph node involvement). The study will enroll 28 patients aged 18 to 75 years with previously untreated, potentially resectable NSCLC classified as stage IIIB-IIIC. Participants will receive a combination of stereotactic body radiation therapy (SBRT) to the primary lung tumor, followed by two cycles of sintilimab (an immunotherapy drug) plus platinum-based chemotherapy before surgery. The main goals of the study are to see whether this treatment can shrink or eliminate cancer in the contralateral mediastinal lymph node (lymph node downstaging) and allow more patients to undergo curative surgery. Secondary goals include assessing pathological response rates, surgical outcomes, survival, and safety. Patients will be closely monitored during and after treatment, with follow-up visits planned for up to 5 years after surgery.

Conditions

Locally Advanced Non-Small Cell Lung Cancer; Stage IIIb Non-small Cell Lung Cancer; Stage IIIC Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Contralateral Mediastinal Lymph Node Downstaging Rate

  From the start of neoadjuvant therapy until post-surgical pathological assessment, approximately 12 weeks.

• Surgical Conversion Rate

  From the start of neoadjuvant therapy until post-surgical pathological assessment, approximately 12 weeks.

Secondary Outcomes (6)

• Major Pathological Response Rate

  At the time of surgical pathological assessment, approximately 12 weeks after the start of neoadjuvant therapy.

• Pathological Complete Response Rate

  At the time of surgical pathological assessment, approximately 12 weeks after the start of neoadjuvant therapy.

• R0 Resection Rate

  At the time of surgical pathological assessment, approximately 12 weeks after the start of neoadjuvant therapy.

• Event-Free Survival

  From enrollment until the first occurrence of an EFS event, assessed up to 5 years.

• Overall Survival

  From enrollment until death from any cause, assessed up to 5 years.

Study Arms (1)

Experimental : neoadjuvant SBRT combined with immunochemotherapy

EXPERIMENTAL

Drug: Sintilimab; Drug: Paclitaxel; Drug: Carboplatin (AUC 5); Drug: Pemetrexed 500 mg/m2; Radiation: Stereotactic body radiotherapy (SBRT); Procedure: non-small cell lung cancer

Interventions

Sintilimab DRUG

Sintilimab is an anti-PD-1 monoclonal antibody. In this study, it is administered intravenously at a fixed dose of 200 mg on Day 1 of each 3-week cycle. Patients receive 2 cycles of sintilimab in combination with platinum-based doublet chemotherapy. The first dose of sintilimab is initiated within 7 days after completion of stereotactic body radiotherapy (SBRT).

Experimental : neoadjuvant SBRT combined with immunochemotherapy

Paclitaxel DRUG

Paclitaxel is a taxane chemotherapeutic agent. In this study, it is specifically used for patients with squamous cell non-small cell lung cancer (NSCLC). It is administered intravenously at a dose of 175 mg/m² on Day 1 of each 3-week cycle. Patients receive 2 cycles of paclitaxel in combination with sintilimab (anti-PD-1 antibody) and carboplatin (platinum-based agent) as part of the neoadjuvant regimen. Standard premedication to prevent hypersensitivity reactions is required prior to each infusion. This systemic chemotherapy phase is initiated within 7 days after the completion of stereotactic body radiotherapy (SBRT) to the primary lung tumor.

Experimental : neoadjuvant SBRT combined with immunochemotherapy

Carboplatin (AUC 5) DRUG

Carboplatin is a platinum-based chemotherapeutic agent. In this study, it serves as the backbone chemotherapy for all patients, regardless of histology. It is administered intravenously on Day 1 of each 3-week cycle. The dose is calculated using the Calvert formula to achieve a target area under the concentration-time curve (AUC) of 5 mg/mL/min. Patients receive 2 cycles of carboplatin in combination with sintilimab (anti-PD-1 antibody) and either pemetrexed (for non-squamous NSCLC) or paclitaxel (for squamous NSCLC). This chemoinmunotherapy phase commences within 7 days after the completion of stereotactic body radiotherapy (SBRT) to the primary lung tumor.

Experimental : neoadjuvant SBRT combined with immunochemotherapy

Pemetrexed 500 mg/m2 DRUG

Pemetrexed is an antifolate chemotherapeutic agent. In this study, it is specifically used for patients with non-squamous non-small cell lung cancer (NSCLC). It is administered intravenously at a dose of 500 mg/m² on Day 1 of each 3-week cycle. Patients receive 2 cycles of pemetrexed in combination with sintilimab (anti-PD-1 antibody) and carboplatin (platinum-based agent) as part of the neoadjuvant regimen. To reduce toxicity risks, standard premedication (including folic acid, vitamin B12 supplementation, and corticosteroids) is required as per the product label. This systemic chemotherapy phase is initiated within 7 days after the completion of stereotactic body radiotherapy (SBRT) to the primary lung tumor.

Experimental : neoadjuvant SBRT combined with immunochemotherapy

Stereotactic body radiotherapy (SBRT) RADIATION

Stereotactic Body Radiotherapy (SBRT) is a precise, high-dose form of external beam radiation therapy. In this study, SBRT is directed only at the primary lung tumor (not the lymph nodes). The treatment is delivered in 3 fractions (sessions) over approximately 3 days, with a total dose of 24 Gy (8 Gy per fraction). Treatment planning is based on 4D-CT simulation to account for respiratory motion. The SBRT is completed before the initiation of systemic therapy (sintilimab + chemotherapy).

Experimental : neoadjuvant SBRT combined with immunochemotherapy

non-small cell lung cancer PROCEDURE

Radical lung resection is the planned definitive treatment for eligible patients. Approximately 4 weeks after neoadjuvant therapy, patients first undergo cervical mediastinoscopy for contralateral lymph node assessment. Only those with negative pathology proceed to surgery 2 weeks later. The surgery involves initial video-assisted thoracoscopic dissection of remaining contralateral nodes (specific stations based on primary tumor side) with intraoperative frozen section. If negative, patients undergo immediate repositioning and radical lung resection (lobectomy/pneumonectomy) with ipsilateral lymphadenectomy(right side dissection of lymph nodes in groups 3A, 9R and 10R, left side dissection of lymph nodes in groups 5, 6, 9L and 10L).

Experimental : neoadjuvant SBRT combined with immunochemotherapy

Eligibility Criteria

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

You may qualify if:

• Voluntary Participation: The patient volunteers to participate and signs a written informed consent form.
• Pathology and Staging: Cytologically or histologically confirmed, previously untreated non-small cell lung cancer (NSCLC) with contralateral mediastinal lymph node involvement (N3), classified as stage IIIB or IIIC according to the 9th edition of the International Association for the Study of Lung Cancer (IASLC) staging manual. Baseline staging must be performed with either PET/CT or a combination of contrast-enhanced CT of chest/abdomen + bone scan + brain MRI.
• Surgical Feasibility: The lung lesion is considered \*\*potentially resectable as evaluated by a multidisciplinary team that includes a thoracic surgeon.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Adequate Organ Function:
• (1) Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L (2) Platelet count ≥ 100 x 10\^9/L (3) Hemoglobin \> 9.0 g/dL (4) Serum creatinine ≤ 1.5 x upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥ 40 mL/min (5) Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤ 3 x ULN (6) Total bilirubin ≤ 1.5 x ULN (7) Forced expiratory volume in 1 second (FEV1) ≥ 1.2 L or \> 40% of predicted value (8) International normalized ratio (INR) and activated partial thromboplastin time (aPTT) within normal limits.
• \. Age: Between 18 and 75 years old.

You may not qualify if:

• Autoimmune Disease: Active or suspected autoimmune disease. Exception: Patients with vitiligo, type I diabetes mellitus, or hypothyroidism requiring only hormone replacement therapy (e.g., Hashimoto's thyroiditis) with no signs of active disease may be enrolled.
• Immunosuppressive Therapy: Requires systemic corticosteroid therapy (\>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to enrollment.
• Prior Chest Radiotherapy: History of prior radiotherapy to the chest.
• Active Bleeding: Presence of clinically significant active bleeding prior to treatment.
• Severe Organ Dysfunction: Severe cardiac, pulmonary, hepatic, or renal dysfunction, hematopoietic system disease, or cachexia, as judged by the investigator to be intolerable to chemo-radiotherapy.
• Poorly Controlled Diabetes: History of diabetes mellitus for \>10 years with unsatisfactory glycemic control.
• Interstitial Lung Disease: History of interstitial lung disease or non-infectious pneumonitis.
• Driver Gene Mutations: NSCLC with known activating EGFR mutations or ALK fusion gene positivity.
• Other Malignancies:
• Excluded: History of other active malignancies within the past 2 years, except for adequately treated non-melanoma skin cancer or carcinoma in situ (e.g., bladder, gastric, colorectal, endometrial, cervical, melanoma, or breast).
• Exception: Patients with other malignancies who have achieved complete remission for ≥2 years and do not require additional anti-tumor therapy during this study may be enrolled.
• Compliance/Understanding: Medical, psychological, or physiological conditions that, in the investigator's judgment, prevent the patient from completing the study or understanding the study information.
• Prior Immune Therapy: Previous treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other drug targeting T-cell co-stimulation or checkpoint pathways.
• Active Viral Infection:
• (1) Active Hepatitis B (HBsAg positive AND HBV DNA ≥ 2000 IU/mL or 10\^4 copies/mL).

Sponsors & Collaborators

• Yang Hong: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sintilimab; Paclitaxel; Carboplatin; Pemetrexed; Radiosurgery

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)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Hong Yang

CONTACT

86+020-87340973; yanghong@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 16, 2025
• First Posted: December 30, 2025
• Study Start: December 31, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2032
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)