Phase 1 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 Biopharma Co., Ltd, which blocks the immune checkpoint PD-1 and TIM-3-mediated immunosuppressive signal pathways, and showed better T/DC cell activity and in vivo anti-tumor efficacy compared to TIM-3 and PD-1 antibody combination in preclinical studies. Here we report the results of the first-in-human, multicenter, open-label, phase I trial of LB1410 monotherapy in pts with advanced solid tumors ( Keyplus-001 ). Methods: Eligible pts were ≥ 18 yr old with ECOG PS 0-1 and previous treatment. Dose escalation cohorts ranged from 0.001 mg/kg to 20 mg/kg IV Q2W: 0.001mg/kg-1mg/kg in an accelerated titration design, and 3 mg/kg-20 mg/kg using traditional 3+3 design. The primary objective is safety, including dose-limiting toxicities (DLTs). Secondary/exploratory objectives include efficacy, pharmacokinetics (PK), and immunogenicity. Data cutoffs were January 5, 2024 for safety, and January 25, 2024 for efficacy. Results: In total, 52 pts received LB1410 from 0.001 mg/kg to 20 mg/kg as of Jan 5, 2024, median age 58 yr, 69% male. All of patients enrolled had multiple organ metastases or multiple metastases in a single organ, and were heavily treated with anti-tumor treatment, 36/52 (69.2%) were resistant to or refractory to PD-1/PD-L1 inhibitors, and 16/52 (30.8%) were MSS CRC. Treatment related AEs (TRAEs) occurred in 65.4% of pts. The most common TRAE was anemia (19.2%). 2 patients developed Gr3 hypokalemia. There were no DLTs. Tumor response evaluation were available in 40 pts: 14 had stable disease, 25 had progression, and 1 was not evaluable. Target lesion shrinkage was observed in 9 pts, including one patient's sum of target lesion reduced by 48.7% from baseline. Of 14 pts who had stable disease, there were 2 pts with stable disease lasting for more than 6 months. PK was generally dose proportional within 1 mg/kg~15 mg/kg, with t 1/2 ~4.12 days in 10 mg/kg, and t 1/2 ~4.77 days in 15 mg/kg. Of the 22 subjects tested for ADA, only one produced ADA for LB1410, the positive rate was 4.5%. Antidrug antibodies had limited impact on PK. As of Jan 5, 2024, 39 pts remained on the study; updated data will be presented. Conclusions: LB1410 has manageable safety and shows preliminary efficacy. Additional dose and efficacy expansion study is ongoing in immunotherapy-naive pts with MSS CRC and pts who are resistant to immunotherapy. Clinical trial information: NCT05357651 .