Iparomlimab and tuvonralimab (PD-1/CTLA-4 bifunctional antibody) monotherapy or combination therapy in patients with advanced solid tumors treated.

Abstract

e23358 Background: Patients with advanced solid tumors that progress after first-line treatment, particularly after PD-(L)1 inhibitor therapy, face limited treatment options. Iparomlimab and Tuvonralimab (QL1706) exert PD-1 inhibition while preserving the ADCC effect of CTLA-4 to deplete Treg cells. the anti-CTLA-4 antibody was engineered to have a shorter elimination half-life (t1/2) to reduce its exposure and lower the risk of irAEs,achieving a balance of enhanced efficacy and reduced toxicity.This multicenter real-world study evaluates the clinical utility of QL1706 in patients with advanced solid tumors, with a particular focus on those receiving 2nd-line and beyond treatments, including in the immunotherapy rechallenge setting. Methods: We enrolled patients with histologically confirmed advanced solid tumors who had received QL1706 (monotherapy or combination) as 2nd-line and beyond treatment across six clinical centers. The primary endpoint was safety. Secondary endpoints included objective response rate (ORR),disease control rate (DCR), progression-free survival (PFS),and overall survival (OS). Results: As of December 31, 2025, 50 patients were evaluable (NSCLC, 24%; gastric, 16%; HCC, 14%; rectal, 14%; others, 32%). In the overall cohort(n = 50; median age 62.0; 70% male),the ORR was 26.0% (13/50; 95% CI, 13.4–38.6) and DCR was 88.0% (44/50; 95% CI, 78.7–97.3) according to RECIST version 1.1.The median PFS and OS have not yet been reached (with a median follow-up of 6.7 months).Robust disease control was maintained across later lines, with ORR of 42.9% (6/14) and DCR of 92.9% (13/14) in 3rd-line settings.In the immunotherapy rechallenge subgroup (n = 32; median age 65.0), QL1706 demonstrated encouraging activity despite prior PD-(L)1 failure, with an ORR of 18.8% (6/32; 95% CI, 4.0–33.1) and a DCR of 84.4% (27/32; 95% CI, 71.1–97.7). At a median follow-up of 6.3 months, median PFS was 7.5 months (95% CI, 4.1–10.9), median OS was not yet reached.In the overall population,immune-related adverse events (irAEs) occurred in 26% of patients. Notably, Grade 3 irAEs were limited to 5.4% (primarily pneumonitis and elevated AST), showing a more favorable safety profile compared to historical anti-PD-1/CTLA-4 combination therapies. No treatment-related deaths were reported. Conclusions: In this study, QL1706 demonstrated a manageable safety profile and encouraging antitumor activity in patients with advanced solid tumors as 2nd-line and beyond treatment.Notably, QL1706 could be a potential treatment regimen for patients receiving immunotherapy rechallenge after prior PD-(L)1 failure. Clinical trial information: ChiCTR2500106339.