Hypofractionated Chemoradiotherapy With Tislelizumab and Surufatinib for Unresectable Stage III NSCLC

A Randomized Phase 2 Study of Hypofractionated Concurrent Chemoradiotherapy Combined With Tislelizumab and Surufatinib in Patients With Unresectable Stage III Non-Small Cell Lung Cancer

This phase II trial employs a prospective, randomized, parallel-group design to evaluate the efficacy and safety of hypofractionated radiotherapy combined with tislelizumab and surufatinib. Eligible patients are randomly assigned to one of two arms: Experimental Group A receives hypofractionated chemoradiotherapy plus concurrent tislelizumab and surufatinib, followed by consolidation therapy with tislelizumab plus surufatinib; Experimental Group B receives the same hypofractionated chemoradiotherapy plus concurrent tislelizumab alone, followed by tislelizumab consolidation.

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC (Non-small Cell Lung Cancer)
• Intervention / Treatment: Radiation: Radiotherapy; Drug: Concurrent chemotherapy; Drug: Tislelizumab; Drug: Surufatinib

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: DaQuan Wang, MD; Phone Number: +862087343031; Email: wangdq@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Sun Yat-sen University Cancer Center
      • Contact: Hui Liu, Doctor; Phone Number: +862087343031; Email: liuhuisysucc@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Males or females aged 18 to 75 years or older;
• Patients must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC);
• Unresectable Stage III disease according to AJCC 8th staging system;
• Negative for known driver gene mutations；
• Newly diagnosed patients or patients treated with ≤ 4 cycles of chemotherapy combined with or without immunotherapy;
• Expected survival ≥ 12 weeks;
• WHO Performance Status (PS) score of 0 or 1;
• Female subjects must not be breastfeeding;
• Women of childbearing potential (WOCBP) must agree to use contraception during the study treatment and for 5 months after the last dose of study drug (i.e., 30 days [one ovulation cycle] plus approximately five half-lives of the study drug);
• Adequate organ and bone marrow function as defined by the following criteria:
• Forced Expiratory Volume in 1 second (FEV1) ≥ 800 mL;
• Absolute neutrophil count ≥ 1.5 × 10⁹/L;
• Platelets ≥ 100 × 10⁹/L;
• Hemoglobin ≥ 9.0 g/dL;
• Creatinine clearance ≥ 50 mL/min as calculated by the Cockcroft-Gault formula (Cockcroft and Gault, 1976);
• Serum bilirubin ≤ 1.5 × upper limit of normal (ULN);
• AST and ALT ≤ 2.5 × ULN.

Exclusion Criteria:

• Concurrent enrolment in another clinical study, unless it is an observational(non-interventional) clinical study;
• Mixed small cell and non-small cell lung cancer histology;
• Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access;
• Active or prior documented autoimmune disease within the past 2 years;
• Active or prior documented inflammatory bowel disease (eg. Crohn's disease, ulcerative colitis);
• History of primary immunodeficiency;
• History of organ transplant that requires therapeutic immunosuppression;
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent;
• Known history of tuberculosis;
• History of another primary malignancy within 5 years prior to starting treatment, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study;
• Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control.

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: Study group A; Patients will receive hypofractionated thoracic radiotherapy with concurrent chemotherapy, combined with tislelizumab and surufatinib during radiotherapy. Patients who achieve complete response, partial response, or stable disease after chemoradiotherapy will receive consolidation therapy with tislelizumab and surufatinib for up to one year.	Radiation: Radiotherapy; Split-course hypofractionated thoracic radiotherapy; Drug: Concurrent chemotherapy; Weekly nab-paclitaxel and cisplatin during radiotherapy; Drug: Tislelizumab; Tislelizumab 200mg every three weeks during and following radiotherapy; Drug: Surufatinib; Surufatinib during and following radiotherapy
Experimental: Study group B; Patients will receive hypofractionated thoracic radiotherapy with concurrent chemotherapy, combined with tislelizumab during radiotherapy. Patients who achieve complete response, partial response, or stable disease after chemoradiotherapy will receive consolidation therapy with tislelizumab for up to one year.	Radiation: Radiotherapy; Split-course hypofractionated thoracic radiotherapy; Drug: Concurrent chemotherapy; Weekly nab-paclitaxel and cisplatin during radiotherapy; Drug: Tislelizumab; Tislelizumab 200mg every three weeks during and following radiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	The time from randomization to the first documented disease progression or death from any cause, whichever occurs first.	18-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The time from randomization to death from any cause, censored at the last follow-up date.	18-month
Treatment related toxicity	Graded by CTCAE 5.0	18-month

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2029

Study Registration Dates

• First Submitted: May 20, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Therapeutics; Radiotherapy; tislelizumab; surufatinib
• Other Study ID Numbers: A2025-007

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