Low-dose radiation and stereotactic body radiotherapy with PD-1 inhibitor sintilimab and chemotherapy for first-line treatment of locally advanced or metastatic squamous lung cancer: protocol for a randomised phase II trial (IHC002 study)

INTRODUCTION: Lung cancer remains a leading cause of cancer-related deaths worldwide, with squamous lung cancer representing a significant subtype. Despite advancements in chemotherapy and immunotherapy, outcomes for patients with advanced squamous lung cancer remain suboptimal. Recent studies have shown that immunotherapy, particularly with programmed death receptor 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, can improve survival rates, but challenges persist in achieving durable responses. Combining immunotherapy with radiotherapy has emerged as a promising strategy. Stereotactic body radiotherapy (SBRT) can enhance the immune response by inducing tumour-specific antigen release and promoting systemic immune activation, while low-dose radiation (LDRT) may further potentiate these effects by modulating the immune environment. This study explores a novel triple-combination approach using SBRT, LDRT, sintilimab and chemotherapy to optimise therapeutic efficacy and improve outcomes in locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC). METHODS AND ANALYSIS: This is a randomised, controlled, open-label, multicentre phase II clinical trial involving patients with locally advanced or metastatic sqNSCLC. Participants are randomised 1:1 into two arms: the experimental arm receives SBRT and LDRT combined with sintilimab and chemotherapy, while the control arm receives sintilimab with chemotherapy alone. Randomisation is stratified by PD-L1 expression and the presence of brain metastases. The primary endpoint is the objective response rate. Secondary endpoints include disease control rate, progression-free survival, overall survival and safety. Based on an expected ORR of 75% for the experimental group and 55% for the control, with a 20% difference detection at 80.1% power and a two-sided α level of 0.2, a total of 114 patients (57 per group, accounting for a 10% dropout rate) is required. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Commission of Sichuan University West China Hospital (2023-1582), Medical Ethics Committee of Affiliated Hospital of North Sichuan Medical College (2024ER543-1), Ethics Committee of The Second Affiliated Hospital of Chongqing Medical University (2024-54-2), Ethics Committee of Union Hospital (Tongji Medical College, Huazhong University of Science and Technology) (2024-1052-02), Ethics Committee of Sichuan Cancer Hospital (SCCHEC-02-2025-069), Clinical Trial Ethics Committee of Deyang People's Hospital (2025-03-012-H01), and Ethics Committee of Guizhou Provincial People's Hospital (2025-108). Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION: NCT06121505.