Background: LAG-3 is an immune checkpoint receptor expressed on activated T cells to negatively regulate these cells, resulted in tumor immune escape. LBL-007, a novel anti-LAG-3 antibody, was developed by screening of a human antibody phage display library and demonstrated specific binding to human LAG-3, stimulation of IL-2 release and blockage of LAG-3 binding to its ligands including MHC II. It has shown that LBL-007 significantly inhibited tumor growth in a mouse MC38 tumor model in hLAG-3 knock-in mice with more pronounced tumor inhibition when combined with an anti-PD-1 antibody. Methods: A phase I, multicenter, open-label and first-in-human study was conducted to evaluate the safety, tolerability, and PK in patients with advanced solid tumors. The dose escalation phase was designed with 6 dose cohorts of LBL-007 at 0.05, 0.25, 1, 3, 6 and 10 mg/kg (iv every 2 weeks), using a modified 3+3 design. Key inclusion criteria included: age≥18 years, histologically/cytologically confirmed advanced solid tumors, failed ≥2 lines of prior standard therapies, ECOG of 0-1, and adequate hematologic, renal, hepatic, and cardiac function. Patients who received anticancer or immunotherapy 4 weeks from first dose of LBL-007 were excluded. The primary endpoints were tolerability and safety. Adverse events (AEs) were graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Any potential efficacy was assessed by objective response rate (ORR) evaluated by CT/MRI per RECIST 1.1. Results: From March 12^th, 2020 to Feb 9^th, 2021, 17 patients were evaluated in this study. There were no dose limiting toxicities (DLTs) at any dose cohorts, and patients were tolerated very well. Overall, there were 129 adverse events (AEs), and 8 events were serious adverse event (SAE), of which 5 were defined as suspected unexpected serious adverse reaction (SUSAR), but most unlikely treatment related AEs (TRAEs). All AEs regardless of attribution included anemia, hypocalcemia, and flu related respiratory infection, etc. The most common AEs were anemia (14, 10.9%), hypocalcemia (6, 4.7%) and thrombocytopenia (4, 3.1%). Totally, there were 8 patients without disease progression, defined as SD at the first evaluation and sustained for 3.5-9 months. The target lesions in 2 of these 8 patients were reduced by 18.9% and 23.2% (both in esophagus cancer). The progression-free survival of these 2 patients was 4.4 and 9.0 months, respectively. Patients are also being enrolled into the indication exploratory phase (3 and 6 mg/kg), testing the combination therapy with an anti-PD-1 antibody in patients with melanoma and other solid tumors. Conclusions: The dose escalation part of the study revealed tolerability of LBL-007 with an impressive safety profile, and potentially some encouraging signs of anti-tumor activities. Clinical trial: Chinaclinicaltrials.org.cn (1900025904). Clinical trial information: CTR20210196.