A double-blind, double-dummy, randomized, controlled phase 3 trial of iparomlimab and tuvonralimab (QL1706) vs QL1604 as consolidation therapy following concurrent or sequential chemoradiotherapy (cCRT/sCRT) in patients (pts) with limited-stage small-cell lung cancer (LS-SCLC).

TPS8133 Background: LS-SCLC is a highly aggressive malignancy with poor prognosis. Positioning effective consolidation strategies is a key focus to improve long-term patient outcomes. Prominently, immune checkpoint inhibitors (ICIs) have emerged as consolidation therapy after cCRT or sCRT for LS-SCLC. QL1706 is a bifunctional antibody against both programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4, and iparomlimab (QL1604) is an anti-PD-1 agent. In previous studies, both QL1706 and QL1604 demonstrated manageable safety profiles. Notably, QL1706 also showed encouraging preliminary anti-tumor signals in SCLC, which indicated the potential as consolidation therapy (Zhao et al. 2023; Huang et al. 2023). This trial aims to compare the efficacy and safety of QL1706 and QL1604 as consolidation therapy in pts with LS-SCLC without progression after cCRT or sCRT. Methods: In this multicenter double-blind double-dummy randomized controlled phase 3 trial (NCT06789796), pts with pathologically-confirmed LS-SCLC per AJCC 8 th edition are recruited. Pts are eligible if aged ≥18 years, with adequate organ function, ECOG PS scored 0 or 1, and do not have disease progression after completion of the requested cCRT or sCRT. Prophylactic cranial irradiation (PCI) is permitted before randomization. Approximately 636 pts are planned to be randomized 1:1 to receive either QL1706 (at 5 mg/kg) plus QL1604 placebo or QL1604 (at a fixed dose of 200 mg or at 3 mg/kg for pts weighing <40 kg) plus QL1706 placebo via intravenous infusion on day 1 in a 21-day cycle. Treatment will be continued until disease progression, intolerable toxicity, initiation of new anti-tumor treatment, withdrawal of informed consent, loss to follow-up, trial termination, or up to 24 months, whichever occurs first. Randomization is stratified by disease stage (I/II vs. III), receipt of PCI (yes vs. no), and the type of CRT (cCRT vs. sCRT). The co-primary endpoints are progression-free survival (PFS) per RECIST v1.1 assessed by blinded independent central review (BICR), and overall survival (OS). Secondary endpoints are investigator-assessed PFS, 1-year and 2-year PFS rates assessed by BICR and investigator, objective response rate, disease control rate, duration of response, 1-year and 2-year OS rates, safety, pharmacokinetics, and immunogenicity. Exploratory endpoints are biomarker assessments and their relationship to efficacy and prognosis, as well as patient-reported outcomes. Overall two-sided Type I error (α=0.05) controlled by fixed-sequence testing: BICR assessed PFS will be tested first, followed by OS if significant. An interim analysis is planned. The study will be conducted across around 79 sites in China, and enrollment is ongoing. Clinical trial information: NCT06789796 .