Neoadjuvant SBRT then sintilimab with chemotherapy for N3-positive locally advanced NSCLC

Neoadjuvant Stereotactic Body Radiotherapy Followed by Sintilimab Plus Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer With Contralateral Mediastinal (N3) Lymph Node Metastasis: A Prospective Phase II Clinical Trial

This approach tests whether focused radiation to the primary lung tumor followed by two cycles of sintilimab plus platinum-based chemotherapy before surgery can shrink N3-positive locally advanced non-small cell lung cancer and enable curative surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: sintilimab, chemotherapy, prednisone, immunotherapy, radiation
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT07309952 on ClinicalTrials.gov

What this trial studies

This Phase II study will enroll 28 adults (ages 18–75) with previously untreated, potentially resectable stage IIIB–IIIC NSCLC with contralateral mediastinal (N3) lymph node involvement. Participants receive stereotactic body radiotherapy (SBRT) to the primary lung lesion, followed by two cycles of sintilimab combined with platinum-based chemotherapy (carboplatin with paclitaxel or pemetrexed depending on histology) prior to planned surgical resection. The primary objective is lymph node downstaging of contralateral mediastinal disease to increase eligibility for curative surgery, with secondary endpoints including pathological response, surgical outcomes, survival, and safety. Patients will undergo baseline and post-treatment imaging and clinical monitoring through surgery and follow-up assessments.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 with previously untreated, potentially resectable stage IIIB–IIIC (N3) NSCLC, an ECOG performance status of 0–1, and adequate blood counts and organ function.

Not a fit: Patients with unresectable tumors, prior systemic therapy for the current lung cancer, poor performance status (ECOG ≥2), or major comorbidities that preclude surgery or chemotherapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this approach could downstage contralateral lymph node disease so more patients can undergo curative surgery and potentially improve long-term outcomes.

How similar studies have performed: Neoadjuvant immunotherapy combined with chemotherapy has shown promising pathological response rates in locally advanced NSCLC and SBRT plus immunotherapy is under active study, but applying this sequence specifically for N3 disease is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Voluntary Participation: The patient volunteers to participate and signs a written informed consent form.
2. 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.
3. Surgical Feasibility: The lung lesion is considered \*\*potentially resectable as evaluated by a multidisciplinary team that includes a thoracic surgeon.
4. Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
5. 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.

6\. Age: Between 18 and 75 years old.

Exclusion Criteria

1. 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.
2. Immunosuppressive Therapy: Requires systemic corticosteroid therapy (\>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to enrollment.
3. Prior Chest Radiotherapy: History of prior radiotherapy to the chest.
4. Active Bleeding: Presence of clinically significant active bleeding prior to treatment.
5. 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.
6. Poorly Controlled Diabetes: History of diabetes mellitus for \>10 years with unsatisfactory glycemic control.
7. Interstitial Lung Disease: History of interstitial lung disease or non-infectious pneumonitis.
8. Driver Gene Mutations: NSCLC with known activating EGFR mutations or ALK fusion gene positivity.
9. 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.
10. 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.
11. 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.
12. Active Viral Infection:

(1) Active Hepatitis B (HBsAg positive AND HBV DNA ≥ 2000 IU/mL or 10\^4 copies/mL).

(2) Active Hepatitis C (HCV antibody positive AND HCV RNA above the lower limit of detection).

13\. HIV/AIDS: Known positive test for human immunodeficiency virus (HIV) or diagnosed acquired immunodeficiency syndrome (AIDS).

14\. Allergy: Known history of hypersensitivity to sintilimab, any of the chemotherapy agents used, or any of their excipients.

15\. Pregnancy/Lactation: Pregnant or breastfeeding women. 16. Metastatic Disease: Presence of supraclavicular lymph node metastasis or distant metastasis.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Hong Yang

Conditions: Locally Advanced Non-Small Cell Lung Cancer, Stage IIIb Non-small Cell Lung Cancer, Stage IIIC Non-Small Cell Lung Cancer