Safety and efficacy of first-line iparomlimab and tuvonralimab (QL1706) plus carboplatin and etoposide in patients with extensive-stage small cell lung cancer: an open-label, single-arm, phase 2 trial (DUBHE-L-209).

Iparomlimab and tuvonralimab (QL1706) is a MabPair product consisting of PD-1 and CTLA-4 monoclonal antibodies. This single-arm, multicenter, phase 2 study assessed the safety and efficacy of first-line QL1706 plus etoposide and carboplatin (EC) for extensive-stage small cell lung cancer (ES-SCLC). Patients with ES-SCLC received QL1706 plus EC every 3 weeks for 4-6 cycles, followed by QL1706 maintenance therapy until disease progression. Primary endpoint was safety. Among 40 patients enrolled, all patients experienced at least one treatment-related adverse event (TRAE). Most TRAEs were hematologic toxicities. Nine patients (22.5%) experienced immune-related adverse events, mostly grade 1-2, with a median time from treatment to the first irAE of 3.1 months (range 0.1-11.0) with a median duration of the irAEs of 1.3 months (range 0.1-10.7). Grade 3 irAEs occurred in 2 (5.0%) patients, one case each for rash and vomiting. No TRAEs leading to death or treatment discontinuation occurred. In 38 patients evaluable for efficacy, the confirmed objective response rate was 92.1% (95% confidence interval [CI] 78.6-98.3). Median progression-free survival (PFS) and overall survival (OS) were 6.0 months (95% CI 5.4-8.3) and 15.8 months (95% CI 11.4-20.0), respectively. In exploratory analyses, the median OS was 20.5 months (95% CI 11.4-not evaluable) in patients with a good lung immune prognostic index status and 19.7 months (95% CI 11.4-22.5) in patients with a combined positive score <1. QL1706 plus EC was well-tolerated and showed promising anti-tumor activity and survival benefit in first-line treatment for ES-SCLC, and warranted further validation in larger scale phase 3 studies.