Phase I/II study of LB1410, a bivalent TIM-3/PD-1 bispecific antibody, in combination with LB4330, a long-acting IL-10, in patients with advanced solid tumors.

Abstract

2626 Background: LB1410 is an anti-PD-1/TIM-3 bispecific antibody (BsAb) developed by L&L Bio Co., Ltd., Shanghai, China. In an ongoing phase I study in patients (pts) with advanced solid tumors (NCT05357651), LB1410 demonstrated an excellent safety profile (RPIID 20 mg/kg) and promising efficacy in various anti-PD-1-resistant solid tumors: ORR 9.1%; DCR 54.5%; n = 66 as of Jan 4, 2026. Antitumor activity was especially notable in anti-PD-1-resistant ccRCC (ORR 11.1%; DCR 77.8%; n = 9) and anti-PD-1-resistant CC (ORR 38.5%; DCR 69.2%; n = 13). LB4330 is a novel, long-acting IL-10 developed by L&L Bio Co., Ltd., Shanghai, China. It is generated by fusing IL-10 to a high-affinity anti-CLDN18.2 antibody and exhibits a significantly extended T 1/2 of 2.3 days. In a completed phase I study (NCT05707676), LB4330 effectively enhanced CD8+ T cell proliferation and activation in cancer pts and achieved a DCR of 36.4% (12/33) in pts with PDAC, CRC and other anti-PD-1-resistant tumors. Given their complementary mechanisms and potential to better enhance antitumor immune activity, a phase I/II study has been launched to evaluate LB1410 in combination with LB4330 in pts with advanced solid tumors. Methods: Eligible pts were ≥18 yrs old with ECOG PS 0-1. Pts received LB1410 at 15 or 20 mg/kg in combination with LB4330 at 0.2-0.4 mg/kg IV Q2W, with a maximum of 6 doses of LB4330. A 3+3 dose-escalation design was used to assess safety and tolerability. The selected doses of LB1410 at 15 or 20 m/kg plus LB4330 at 0.4 mg/kg were used for the efficacy expansion study in pts with anti-PD-1-resistant ccRCC and HCC. Results: As of Jan 14, 2026, 15 patients (1 CRC, 1 HCC, 3 NSCLC, 4 CC and 6 ccRCC) had been enrolled: median age 58.5 yrs (42-71 yrs); 57.1% male; 85.7% with prior anti-PD(L)1-based therapies. TRAEs occurred in 13 pts (92.9%), the most common (≥ 20%) being fever, platelet count decreased, pruritus, elevated ALT, elevated AST, elevated creatinine, cough, rash and anemia. Most TRAEs were related to the MOA of LB4330 and were manageable. Grade 3-4 TRAEs occurred in 5 pts (35.7%), including decreased platelet count in 2 pts and IRR, shock symptom and immune-mediated myocarditis in 1 pt each. No DLTs were observed. Among all pts with on-treatment scans, the overall ORR per RECIST 1.1 was 15.4% (2/13) with 2 confirmed PR ; DCR was 30.8% (4/13). Notably, the 5 pts with anti-PD-(L)1-refractory favorable-risk ccRCC showed an ORR of 40.0% and a DCR of 80.0%. 50% ccRCC pts with PR/SD (2/4) had been on treatment for nearly one year or longer. Conclusions: The combination of LB1410 and LB4330 exhibited a manageable safety profile consistent with that observed with each monotherapy. Clinical data in pts with favorable-risk ccRCC support the characteristics and efficacy of LB4330 as an immune-enhancing agent. Efficacy expansion studies are ongoing. Clinical trial information: NCT06468358 .