Single-center phase 2 trial of iparomlimab and tuvonralimab with definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma

Definitive chemoradiotherapy (CRT) is the standard treatment for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). However, the prognosis of these patients remains poor. The phase 2 QL1706-IIT-02 trial, at Tianjin Medical University (China), evaluated iparomlimab and tuvonralimab (QL1706), a novel PD-1/CTLA-4 dual inhibitor, combined with definitive CRT in patients with unresectable stage III-IVA ESCC. Patients received radiotherapy (50.4 Gy in 28 fractions on 5 days per week), two 3-week cycles of paclitaxel plus cisplatin, and 3-week cycles of QL1706 for up to 1 year. The primary endpoint was progression-free survival (PFS). Twenty of 39 patients (51.3%) completed 18 cycles of QL-1706. With a median follow-up of 21.1 months, the median PFS was 14.8 months (95% CI 11.2-NA), while the median overall survival (OS) data were immature. The 1-year PFS and OS rates were 58.6% and 84.6%, respectively. The objective response rate and median duration of response were 84.6% and 12.7 months. Grade ≥ 3 adverse events occurred in 89.7% of the patients, predominantly lymphopenia. The authors conclude that QLq706 combined with CRT demonstrated potential antitumor activity and manageable toxicity, supporting further investigation.