Stereotactic Body Radiotherapy Followed by Tislelizumab Plus Platinum-based Chemotherapy Versus Tislelizumab Plus Platinum-based Chemotherapy as Neoadjuvant Therapy in Patients With Resectable Stage Ⅱ-Ⅲ Non-small Cell Lung Cancer: A Phase Ⅲ, Randomized, Multicenter, Prospective Study (SACTION2401)

The goal of this clinical trial is to compare the efficacy and safety of neoadjuvant Stereotactic Body Radiotherapy (SBRT) combined with immunochemotherapy versus neoadjuvant immunochemotherapy. The main questions it aims to answer are:

Dose SBRT combined with immunochemotherapy improve event-free survival? Is SBRT combined with immunochemotherapy safe enough?

Participants will:

Receive neoadjuvant SBRT combined with immunochemotherapy or neoadjuvant immunochemotherapy.

Tumor assessment will be performed prior to surgery. Surgery will be performed within 4 to 6 weeks (+ 7 days) after completion of the last cycle of immunochemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer (NSCLC)
• Intervention / Treatment: Radiation: Stereotactic body radiotherapy (SBRT); Drug: Tislelizumab; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Hong Yang, MD; Phone Number: 020-87343932 86-020-87343932; Email: yanghong@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun yat-sen University Cancer Center
      • Contact: Hong Yang, M.D., PH.D.; Phone Number: 00+86+02087343258; Email: yanghong@sysucc.org.cn
      • Contact: Jiyang Chen, Bachelor; Phone Number: 00+86+02087343932; Email: chenjy1@sysucc.org.cn
      • Principal Investigator: Hong Yang, M.D., PH.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Patients voluntarily agree to participate and sign the informed consent; 2. Patients with cytologically/histologically diagnosed (by means of percutaneous lung aspiration biopsy, bronchoscopy, mediastinoscopy, etc.), untreated stage IIa-IIIa (according to the AJCC 8th edition of thoracic tumor staging) non-small cell lung cancer. In addition, patients with potentially resectable stage IIIb (T3-4N2) NSCLC will also be enrolled. All patients are required to receive PET/CT (or chest + upper abdominal CT + brain MRI) at baseline for clinical staging; 3. Pulmonary lesions will be assessed as resectable/potentially resectable by a multiple disciplinary team including thoracic surgeon; 4. Eastern Cooperative Oncology Group Performance Status 0 to 1 5. Requirements for hematology: i, neutrophils ≥ 1500 x 109/L; ii, platelets ≥ 100 x 109/L; iii, hemoglobin > 9.0 g/dL; iv, serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min; v, aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 3 x ULN; vi, total bilirubin ≤ 1.5 x ULN; vii. forced expiratory volume in the first second (FEV1) ≥ 1.2 L or > 40% predicted; viii. International Normalized Ratio/activated partial thromboplastin time (INR/APTT) within the normal range; 6. Age 18-75

Exclusion Criteria:

• 1. Patients with or suspected with autoimmune diseases. Note: patients with vitiligo, type 1 diabetes, hypothyroidism managed with hormone replacement therapy only (Hashimoto's thyroiditis) can be enrolled in the study when there is no clear evidence of recurrence; 2. Patients required systemic corticosteroids treatment (dose > 10 mg daily prednisolone [or equivalent]) or other immunosuppressive drugs within 14 days of enrollment. Note: inhaled or topical corticosteroids, or adrenal replacement therapy (dose > 10 mg daily prednisolone [or equivalent]) are acceptable for patients without apparent autoimmune disease; 3. Historical radiotherapy of chest 4. Active bleeding before treatment 5. Patents with sever heart, lung, liver, or kidney insufficiency 6. Diabetes more than 10-year; unsatisfactory blood glucose control 7. Patients with interstitial lung disease or non-infectious pneumonia 8. EGFR-mutations and ALK-fusion positive NSCLC 9. Patients with other prior malignancies (except skin malignancies other than non-melanoma, and carcinoma in situ at the following sites [bladder, stomach, colorectal, endometrium, cervix, melanoma, or breast]) are not eligible for enrollment in this study. However, if the prior malignancies remain in complete response (CR) for ≥ 2 years and no additional anti-cancer therapy is required during the study, such patients are permitted to be enrolled; 10. The patient is medically, psychologically, or physiologically unable to complete the study or to understand the Patient Information Sheet, in the opinion of the investigator; 11. Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA any other drugs specifically targeting T-cell co-stimulation or immunoregulation pathways; 12. Present active hepatitis B or hepatitis C 13. Patients with positive HIV test results or diagnosed with acquired immunodeficiency disease (AIDS); 14. Hypersensitivity to the investigational product; 15. Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: neoadjuvant SBRT combined with immunochemotherapy; Following admission, intrapulmonary primary stereotactic body radiotherapy (SBRT) was administered at a dosage of 24 Gy across three fractions. Subsequently, within seven days of completing SBRT, two cycles of Tislelizumab in combination with a platinum-based double-agent chemotherapy regimen were initiated. These cycles were repeated every three weeks. Surgical intervention was scheduled to occur 4-6 weeks (±7 days) after the completion of the second chemotherapy cycle	Radiation: Stereotactic body radiotherapy (SBRT); Radiation source: 6MV photon linear gas pedal is used. Position immobilization: supine position, hands up, vacuum bag or styrofoam immobilization. Radiotherapy plan design: 4DCT positioning, radiotherapy plan design at 20% respiratory time-phase CT, isocentric irradiation, IMRT or VMAT design. Definition of target area: Gross tumor volume (GTV) includes the primary tumor in the lung, excluding lymph nodes. Internal target volume (ITV); Internal target volume (ITV) is formed by the fusion of 10 respiratory phases of GTV; Planning target volume (PTV) is formed by expanding the ITV by 0.5 cm in all directions.; Other Names: SBRT; Drug: Tislelizumab; PD-L1 inhibitor; Drug: Chemotherapy; platinum-based double-agent chemotherapy
Active Comparator: neoadjuvant immunochemotherapy; Three cycles of Tislelizumab in conjunction with platinum-based chemotherapy were administered at three-week intervals. Surgical intervention was subsequently scheduled to occur within 4 to 6 weeks (±7 days) following the completion of the third chemotherapy cycle.	Drug: Tislelizumab; PD-L1 inhibitor; Drug: Chemotherapy; platinum-based double-agent chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
event-free survival	include 2/3/5 event-free survival time	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major pathologic response (MPR) rate		1-year
pathological complete response (PCR) rates		1-year
R0-resection rate		1-year
overall survival	2/3/5 years overall survival rate	5 years
safety	adverse events rate, postoperative complication rate, mortality rate.	1-year

Collaborators and Investigators

• Sponsor: Yang Hong

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2024
• Primary Completion (Estimated): January 30, 2027
• Study Completion (Estimated): January 30, 2030

Study Registration Dates

• First Submitted: September 14, 2024
• First Submitted That Met QC Criteria: September 14, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Actual): May 29, 2025
• Last Update Submitted That Met QC Criteria: May 22, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; immunochemotherapy; SBRT
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Tislelizumab
• Other Study ID Numbers: B2024-495-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No