Combining SBRT with GM-CSF and peg-IFNα to induce abscopal effects in previously treated patients with stage IV thymic tumors: A single arm, single center, phase II trial.

8110 Background: After the failure of first-line treatment, patients with stage IV thymic tumors have a poor prognosis and few therapeutic options. Combining stereotactic body radiotherapy (SBRT) with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Pegylated interferon-α (Peg-IFNα) may induce abscopal effects and improve prognosis. Methods: We conducted this open-label, single-arm single center, phase Ⅱ trial to evaluate SBRT plus GM-CSF and Peg-IFNα in previously treated patients with stage Ⅳ thymic tumors. A 21-day treatment cycle consisted of SBRT delivered to one metastatic lesion with 30 Gy in 5 fractions from day 1, synchronous subcutaneous injection of GM-CSF 125 μg/ m 2 once daily for 14 days, and subcutaneous injection of Peg-IFNα 90 μg on day 8. If the patient has more than two metastatic lesions, another treatment cycle was repeated. After the completion of 1 or 2 treatment cycles, Peg-IFNα therapy was maintained for at least half a year with a subcutaneous injection of 90 μg once a month. The two primary endpoints were the proportion of patients with abscopal effects and the objective response rate (ORR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), and therapeutic safety. Results: A total of 27 patients were enrolled in the trial from March 2021 to September 2024. One patient died of cardiac arrest before ORR evaluation during COVID-19 pandemic and was excluded, leaving 26 patients in the analysis, with 1 (3.8%) type A thymoma, 1 (3.8%) type AB thymoma,4 (15.4%) type B1 thymoma, 3 (11.5%) type B2 thymoma, 1 (3.8%) type B3 thymoma, 1 (3.8%) type B2+B3 thymoma, 13 (50.0%) thymic squamous cell carcinoma and 2 (7.7%) thymic neuroendocrine tumor. At a median follow-up of 26.4 months, 8 (30.8%) out of 26 patients had abscopal effects, and the ORR was 38.5%. The median OS for patients with abscopal effect has not been attained yet. The median PFS was 13.0 months. We observed that patients with abscopal effects tended to have longer OS and PFS than those without abscopal effects. 5 patients (19.2%) experienced Grade 3 treatment-related adverse events (CTCAE version 5.0). Conclusions: Combining SBRT with GM-CSF and Peg-IFNα was well tolerated with acceptable toxicity and may represent a promising salvage therapy for previously treated patients with stage IV thymic tumors. The occurrence of abscopal effects is likely to improve patient outcomes. Clinical trial information: NCT04517539 .