Phase I study of LB1410, a bivalent TIM-3/PD-1 bispecific antibody, in patients with advanced solid tumors.

2639 Background: LB1410 is a recombinant humanized anti-PD-1/TIM-3 bispecific antibody (BsAb) developed by L&L Bio Co., Ltd, Shanghai, China for patients (pts) resistant/refractory (R/R) to anti-PD-(L)1 therapies. Pre-clinical studies revealed superior T cell and DC activity and in vivo antitumor efficacy compared to the combined use of TIM-3 and PD-1 monoclonal antibodies. This ongoing open-label phase I trial evaluates LB1410 monotherapy in pts with advanced solid tumors. Methods: Eligible pts were ≥18 yrs old with ECOG PS 0-1. Dose ranged from 0.001 to 20 mg/kg IV Q2W or 2000 mg/kg IV Q3W in an accelerated titration or a traditional 3+3 design. The RPIID of 20 mg/kg was used for efficacy expansion in pts with advanced clear cell renal cell carcinoma (ccRCC), cervical cancer (CC) and hepatocellular carcinoma (HCC). The primary objective was safety, including dose-limiting toxicities (DLTs); secondary objectives included efficacy, pharmacokinetics (PK) and immunogenicity. Results: As of Jan 4, 2026, 94 pts were enrolled: median age 59 yrs (31-73 yrs); 64.9% male; 84.0% ECOG PS 1. Tumor types included NSCLC (26.6%), CRC (21.3%, all non-MSI-H), CC (14.9%), ccRCC (11.7%), HCC (9.6%) and others (16.0%). 77 pts (81.9%) had received ≥ 2 prior lines of therapy. 98.6% non-CRC pts (73/74) were R/R to anti-PD-(L)1 therapies. 72 pts (76.6%) experienced TRAEs. The most common TRAEs (≥ 10%) included anemia (25.5%), proteinuria (11.7%), elevated ALT (11.7%), elevated AST (11.7%) and elevated lactate dehydrogenase (10.6%). Only 10 pts (10.6%) experienced Grade 3-4 TRAEs, most frequently hypertension (4.3%) and hypokalemia (2.1%). Only 1 hypertension and 1 elevated GGT in 1 pt were Grade 4. Serious TRAEs occurred in 3 pts (3.2%). No DLTs were observed. Among pts with available on-treatment scans, the overall ORR per RECIST 1.1 was 7.1% (6/85) with 5 confirmed PRs and 1 confirmed CR; the DCR was 48.2% (41/85). Notably, among CC pts previously treated with anti-PD-(L)1 therapies, there were 4 confirmed PRs and 1 confirmed CR: ORR 38.5% (5/13); DCR 69.2% (9/13); mPFS 7.5 months. 5 pts with CR/PR/SD remained on treatment (max. 16 treatment cycles; max. follow-up 14.4 months). The CR patient had received 5 prior lines of therapy, including PD-1/CTLA-4 BsAb. In anti-PD-1-resistant ccRCC, LB1410 monotherapy had an ORR of 11.1% (1/9) and a DCR of 77.8% (7/9). Conclusions: LB1410 showed an excellent safety profile and promising antitumor efficacy in pts with immune-oncology (IO)-R/R CC. Further studies of LB1410 as monotherapy and in combination with lenvatinib in pts with IO-R/R CC are ongoing. Clinical trial information: NCT05357651 .