Background: HLX26 is a novel humanized anti-LAG3 monoclonal antibody. This study aimed to evaluate the safety, tolerability, and pharmacokinetics of HLX26 in patients with advanced or metastatic solid tumors or lymphomas. Methods: This was a first-in-class, multicenter, open-label, dose-escalation phase 1 study. Patients with histologically or cytologically confirmed advanced solid tumors or lymphomas who had failed or were not suitable for standard therapies were enrolled and received HLX26 at five dose levels (60, 150, 300, 500, or 800 mg, Q3W) intravenously. This study followed accelerated titration combined with a “3+3” design. HLX26 was given until disease progression with no clinical benefit, 2 years of treatment, experiencing intolerable toxicity, withdrawal of consent, or death, whichever occurred first. The primary endpoints were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) within DLT observation period, which was 3 weeks after the first dose of HLX26. Secondary endpoints included safety, pharmacokinetic and pharmacodynamic characteristics, preliminary efficacy, immunogenicity, and potential biomarker explorations of HLX26. Results: As of December 22, 2022, 12 patients with stage IV breast (n = 10, 83.3%) or rectum (n = 2, 16.7%) solid tumors were enrolled and received HLX26 at 60 mg (n = 1), 150 mg (n = 1), 300 mg (n = 3), 500 mg (n = 3), or 800 mg (n = 4). The mean age was 57.5 (range 31–73) years. No DLT was reported and the MTD was not determined as of yet. Eleven (91.7%) patients experienced treatment-emergent adverse events (TEAEs), most commonly hypercholesterolemia (41.7%), hypertriglyceridemia (25.0%), and hyperuricemia (25.0%). Most TEAEs were grade 1 (n = 8, 66.7%) and 2 (n = 2, 16.7%). Conclusions: In summary, no new safety signals were observed from 60 mg to 800 mg of HLX26. HLX26 was safe and well tolerated in patients with advanced or metastatic solid tumors. Clinical trial information: NCT05078593.