2188P First-line combination of toripalimab and chemotherapy in advanced thymic carcinoma: A prospective, single-arm, phase II trial

Thymic carcinomas (TCs) are the most aggressive subtype of thymic epithelial tumors. Chemotherapy is the standard treatment for advanced TCs, although achieved a response less than 50%. Immunotherapy has been crucial in the treatment of several malignancies. Here we conducted a phase II, prospective trial to explore the safety and feasibility of toripalimab (a PD-1 inhibitor) plus chemotherapy as first-line treatment in advanced TCs. We enrolled patients with ECOG 0 or 1, histologically diagnosis of Masaoka stage III or IV TCs. Patients received toripalimab (240mg, d1, q3w) plus paclitaxel (175mg/m2, d1, q3w) and carboplatin (AUC=5, d1, q3w) for 4-6 cycles and continued to receive toripalimab (240mg, d1, q4w) maintenance therapy until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), Disease control rate (DCR), duration of response (DoR), overall survival (OS), time to response (TTR) and safety. This study is registered on chinadrugtrials.org.cn, ChiCTR2000039155. From December 2020 to April 2023, a total of 14 patients (median age: 49, range: 37-68; male: 57.1%) were enrolled. 57.1% of patients were still on treatment (toripalimab maintenance) at the time of analysis. For 12 patients received radiological assessment, 5 partial responses, 7 stable diseases were observed. The ORR was 41.7% and DCR was 100.0%. The median follow-up duration was 7.0 months (range: 0.1-30). Treatment-related adverse events (TRAEs) of any-grade occurred in 13 patients. Grade 3-4 TRAEs occurred in 5 patients (35.7%). The most common grade 3-4 TRAE was myelosuppression (28.6%). Besides, we analyzed the PD-L1 expression, immune microenvironments and genetic mutations in 8 patients' tissues and serum samples using NGS and mIHC. We found that patients with lower TMB had more CD8+T cells and CD56dim NK subtype. Patients with PD-L1 TPS≥1% had a higher proportion of M1 type macrophages, suggesting a greater potential for activating antitumor immunity. Toripalimab combined with chemotherapy is effective and well tolerated as first-line treatment for patients with advanced TCs.