Sintilimab, stereotactic body radiotherapy and granulocyte-macrophage colony stimulating factor as second-line therapy for advanced non-small cell lung cancer: safety run-in results of a multicenter, single-arm, phase II trial


Objectives: The SWORD trial is the first multicenter, single arm, phase II study assessing the safety and efficacy of a PD-1 inhibitor (Sintilimab), stereotactic body radiotherapy (SBRT) and granulocyte-macrophage colony stimulating factor (GM-CSF) in advanced non-small cell lung cancer (NSCLC) without sensitizing driver mutations. A safety run-in phase was conducted to determine the tolerability of the experimental treatment.

Materials and methods: Twenty metastatic NSCLC patients who failed first-line chemotherapy were enrolled, and they received SBRT (8 Gy × 3) to one lesion, followed by Sintilimab (200 mg d1, every 3 weeks, until disease progression, unacceptable toxicity, or up to 35 cycles) and GM-CSF (125 μg/m2 d1-d14, cycle 1) within 2 weeks after SBRT. In addition, blood and tissue samples were serially collected for translational research.

Results: Median age of the patients was 61 and all of them had more than 5 lesions at baseline. The sites of SBRT included lung (n = 11), mediastinal lymph node (n = 5), liver (n = 1), abdominal lymph node (n = 1), pleural nodule (n = 1) and vertebra (n = 1). No patients had dose-limiting toxicities (DLTs) and 18 patients experienced treatment-related adverse event (TRAE). The most common TRAEs were fatigue (50%), fever (30%), and ostealgia (20%), and they all were grade 1. Only 2 grade 3 TRAEs were observed, including elevation of liver enzymes in one and transient acute heart failure in another. No grade 4 or 5 AE was observed.

Conclusion: Sintilimab, SBRT and GM-CSF for advanced NSCLC is safe with manageable TRAEs and the trial continues to recruit participants. Trial registration, NCT04106180. Registered 26 September 2019, SBRT in Combination With Sintilimab and GM-CSF for the Treatment of Advanced NSCLC-Tabular