Neoadjuvant SF-SBRT Plus Toripalimab and Chemotherapy in Resectable Stage II-III NSCLC.

NCT07608159 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: L26-517
• Study Type: interventional
• Target: 201
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, randomized, controlled, multicenter phase III clinical trial designed to evaluate the efficacy and safety of spatially fractionated stereotactic body radiotherapy (SF-SBRT) combined with toripalimab and platinum-based chemotherapy versus toripalimab combined with platinum-based chemotherapy in patients with resectable or potentially resectable stage II-III non-small cell lung cancer (NSCLC). Eligible participants will be randomized 2:1 to receive either neoadjuvant SF-SBRT followed by toripalimab and platinum-based chemotherapy for two cycles, or toripalimab and platinum-based chemotherapy for three cycles. Randomization will be stratified by disease stage and histological subtype. Surgery is planned 4-6 weeks after completion of neoadjuvant treatment, and postoperative adjuvant therapy will be determined by the investigator. The primary endpoint is the 2-year event-free survival rate. Secondary endpoints include pathological complete response rate, major pathological response rate, objective response rate, R0 resection rate, event-free survival, overall survival, and safety. Adverse events will be assessed according to NCI CTCAE version 5.0 or later.

Conditions

Non Small Cell Lung Cancer; Stereotactic Body Radiotherapy; Neoadjuvant Chemoimmunotherapy; Surgery

Keywords

Spatially fractionated radiotherapy; stereotactic body radiotherapy; non small cell lung cancer; neoadjuvant chemoimmunotherapy

Outcome Measures

Primary Outcomes (1)

• 2-year event-free survival rate

  2-year event-free survival rate

  2-year event-free survival rate

Study Arms (2)

neoadjuvant SF-SBRT followed by toripalimab and platinum-based chemotherapy

EXPERIMENTAL

neoadjuvant SF-SBRT followed by toripalimab and platinum-based chemotherapy

Radiation: Stereotactic body radiotherapy (SBRT); Drug: neoadjuvant immunotherapy; Drug: Neoadjuvant Chemotherapy

toripalimab and platinum-based chemotherapy

ACTIVE COMPARATOR

toripalimab and platinum-based chemotherapy

Drug: neoadjuvant immunotherapy; Drug: Neoadjuvant Chemotherapy

Interventions

Stereotactic body radiotherapy (SBRT) RADIATION

spatially fractionated stereotactic body radiotherapy

neoadjuvant SF-SBRT followed by toripalimab and platinum-based chemotherapy

neoadjuvant immunotherapy DRUG

Toripalimab IV (dose 240mg) Q3W

neoadjuvant SF-SBRT followed by toripalimab and platinum-based chemotherapy; toripalimab and platinum-based chemotherapy

Neoadjuvant Chemotherapy DRUG

Squamous cell carcinoma: Paclitaxel (175mg/m²) or Docetaxel (60-75 mg/m²) or Nab-paclitaxel (260mg/m²) plus Carboplatin (AUC=5)/Cisplatin (75 mg/m²) (to be determined by researchers); Non-squamous cell carcinoma: Pemetrexed (500mg/m²) plus Carboplatin/Cisplatin (to be determined by researchers)

neoadjuvant SF-SBRT followed by toripalimab and platinum-based chemotherapy; toripalimab and platinum-based chemotherapy

Eligibility Criteria

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

You may qualify if:

• Male or female participants aged 18 to 75 years;
• Eastern Cooperative Oncology Group performance status of 0 or 1;
• Previously untreated, pathologically confirmed, resectable or potentially -resectable stage II, IIIA, or IIIB (N2) non-small cell lung cancer according to the 8th edition of the American Joint Committee on Cancer staging system;
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1;
• Adequate pulmonary function, as assessed by the surgeon, to tolerate the planned lung resection;
• Absence of sensitizing EGFR mutations or ALK rearrangements confirmed by tissue-based molecular pathological testing;
• Adequate organ function, defined as follows:
• Bone marrow function: absolute neutrophil count ≥1.5 × 10\^9/L, platelet count ≥80 × 10\^9/L, and hemoglobin ≥9 g/dL; Liver function: total serum bilirubin ≤1.5 × upper limit of normal; alanine aminotransferase and aspartate aminotransferase ≤1.5 × upper limit of normal; Renal function: serum creatinine ≤1.5 × upper limit of normal or creatinine clearance ≥60 mL/min, and blood urea nitrogen ≤200 mg/L;
• Participants must be fully informed about the study and voluntarily sign the written informed consent form.
• Male participants with reproductive potential or female participants of childbearing potential must agree to use effective contraception during the study, such as oral contraceptives, an intrauterine device, or a barrier method combined with spermicide, and continue contraception for 6 months after completion of treatment.

You may not qualify if:

• Locally advanced unresectable or metastatic disease. Unresectable disease is defined according to the multidisciplinary consensus for stage III non-small cell lung cancer (2019 edition), including some stage IIIA, stage IIIB, and all stage IIIC disease. This usually includes N2 disease with a single-station mediastinal lymph node with a short-axis diameter ≥3 cm, or multistation lymph node fusion/conglomeration with lymph nodes having a short-axis diameter ≥2 cm on CT; T4 disease invading the esophagus, heart, aorta, or pulmonary veins; and all N3 disease;
• Non-small cell lung cancer involving the superior sulcus, large-cell neuroendocrine carcinoma, or sarcomatoid carcinoma;
• Known sensitizing EGFR mutation or ALK rearrangement. For participants with non-squamous histology, EGFR and ALK mutation status must be confirmed;
• Prior treatment with PD-1 or PD-L1 inhibitors, or agents targeting another T-cell receptor pathway, such as CTLA-4 or OX-40;
• Active or suspected active autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. Exceptions include type 1 diabetes mellitus or hypothyroidism controlled with stable replacement therapy, and dermatologic conditions not requiring systemic treatment, such as psoriasis or vitiligo;
• History of interstitial lung disease of grade 2 or higher;
• Use of systemic corticosteroids, defined as prednisone \>10 mg/day or equivalent, or other immunosuppressive medications within 14 days before the first dose of study treatment;
• History of immunodeficiency, including acquired or congenital immunodeficiency disorders, history of organ transplantation, or prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
• Receipt of a live vaccine within 4 weeks before the first dose of study treatment;
• Severe cardiovascular or cerebrovascular disease, including:
• Poorly controlled hypertension or pulmonary hypertension;
• Unstable angina, myocardial infarction, coronary artery bypass grafting, or coronary stent implantation within 6 months before study treatment;
• Chronic heart failure with New York Heart Association class II or higher cardiac function;
• Left ventricular ejection fraction \<50%;
• Severe arrhythmias requiring medical treatment, except atrial fibrillation or paroxysmal supraventricular tachycardia. Examples include QTcF \>450 msec in males or \>470 msec in females, complete left bundle branch block, or third-degree atrioventricular block;

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiosurgery; Neoadjuvant Therapy

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)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Combined Modality Therapy

Central Study Contacts

Di Liu

CONTACT

+8617621320272; liudi_2012@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Department of Radiation Oncology

Study Record Dates

• First Submitted: May 19, 2026
• First Posted: May 27, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2030
• Last Updated: May 29, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share