Phase I study of IMM2510, a PD-L1/ VEGF bispecific antibody, in participants with advanced IO-treated SQ-NSCLC.

Abstract

8580 Background: Despite advancements in first-line treatments such as immunotherapy and targeted therapies, resistance to these treatments is common, especially those IO-treated and low PD-L1 TPS, creating a significant unmet need for effective second-line therapies. IMM2510 is a bispecific fusion protein targeting PD-L1 and VEGF which can modify tumor microenvironment to overcome resistance and improve sensibility to antitumor agents. The data of dose-escalation phase I was previously reported in ASCO2024. Here we summarize the updated efficacy and safety results of IMM2510 in advanced IO-treated SQ-NSCLC. Part of the data were previously reported in WCLC 2025. Methods: The phase I study was designed as a first-in-human, open-label, multi-center study to evaluate the safety, efficacy, PK and PD of IMM2510 in pts with advanced solid tumors. Eligible pts were enrolled to receive IMM2510 via intravenous infusion Q2W. Results: As of 31 Dec 2025, 32 pts with advanced IO-treated SQ-NSCLC received IMM2510. The median age was 61 years; 31.3% pts had PD-L1 TPS < 1%; 75.0% pts had ECOG score of 1; the median prior lines of anti-tumor therapy were 2 (range: 1-5). All 32 pts experienced TEAEs. Grade ≥3 TEAEs were reported by 17 (53.1%) pts; Grade ≥3 TRAEs were reported by 12 (37.5%) pts; TRAEs leading to treatment discontinuation were reported by 1 (3.1%) participant. No participant experienced TRAE leading to death. 22 pts with advanced IO-treated SQ-NSCLC were evaluable for efficacy analysis. The ORR was 27.3% (6/22) and DCR was 81.8% (18/22). The median DoR was 11.1 months. The median PFS was 9.4 months at the median follow-up time of 8.3 months. The median overall survival was not reached. Exposure-response (ER) analysis within the 3 - 20 mg/kg dose range revealed a positive exposure-efficacy relationship in pts with SQ-NSCLC, with higher exposure corresponding to increased ORR or DCR, while a relatively flat ER was observed for Grade 3 or higher TRAE and most common AEs in NSCLC. Thus, 20 mg/kg Q2W was selected as the RP2D with well-balanced efficacy-safety profiles. Conclusions: In pts with advanced IO-treated SQ-NSCLC, IMM2510 provides clinical meaningful benefit and supports a favorable benefit-risk profile. The phase III clinical study is being planned. Clinical trial information: NCT05972460 .