1414P - Iparomlimab and tuvonralimab (QL1706) with definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma: An open-label phase II study

Background

Definitive concurrent chemoradiotherapy (CCRT) is the standard care for patients with inoperable locally advanced esophageal squamous cell carcinoma (ESCC). However, the survival remains poor. Double blocking PD-1 and CTLA-4 showed efficacy in advanced ESCC. We firstly investigated the safety and feasibility of combining CCRT with QL1706, a single bifunctional MabPair product against PD-1 and CTLA-4, as first-line treatment for these patients.

Methods

Patients with locally advanced ESCC received 2 cycles of paclitaxel, cisplatin and QL1706 every 3 weeks with concurrent radiotherapy (50.4 Gy/28 fractions). After completing CCRT, QL1706 (5 mg/kg) maintained every 3 weeks for one year after enrollment. Primary end point was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. Candidate biomarkers in tumor and peripheral blood were monitored at baseline and after 41.4 Gy radiation.

Results

Between Aug 2022 and Sep 2023, 39 patients were enrolled and analyzed. The median age was 64 years (range, 42-75 years), and men were predominant (79.5%). 29 patient was at stage III, and 10 patients were at stage IVa. With a median follow-up time of 12.2 months (95% CI: 10.9–13.6), the 12-month PFS and OS rates were 62.1% and 86.2%, respectively. Patients with PD-L1–positive tumors (TPS ≥ 5%: 41.0%; CPS ≥ 10: 56.4%) had significantly longer PFS compared with those with PD-L1–negative tumors (HR: 0.273, 95% CI: 0.077-0.969, P = 0.045; HR: 0.284, 95% CI: 0.093-0.867, P = 0.027). OS analysis was immature. The most common treatment-related ≥3 grade adverse events included lymphopenia (79.5%), leukopenia (46.2%), neutropenia (38.5%), thrombocytopenia (10.3%), anemia (7.7%) and pneumonia (5.1%). One patient died of COVID-19 and another patient died of upper gastrointestinal bleeding during QL1706 maintenance. Candidate biomarkers’ analysis is ongoing.

Conclusions

First line CCRT plus QL1706 had a manageable safety profile and promising antitumour efficacy for ESCC and deserves further study. PD-L1 expression had strong predictive value in the study population.

Clinical trial identification

NCT05490719.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

National Natural Science Foundation of China: 82272733,82273083, 82102835, 82373208.

Disclosure

All authors have declared no conflicts of interest.