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Purpose: QL1706 (PSB205) is a novel biological entity consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1) that are expressed together in a fixed ratio from the same production cell line and manufactured as one product. In this Phase I, multiple-dose study (NCT04296994), the tolerability, safety, pharmacokinetics, and preliminary clinical activity of QL1706 in patients with advanced malignant tumors were evaluated. Experimental Design: Dose-escalation was based on an accelerated 3 + 3 design for doses of QL1706 from 0.3 to 10 mg/kg that was administered intravenously every 3 weeks (q3w). The expansion stage was carried out in selected dose cohorts. The primary objective of this study was to define the safety and tolerability of QL1706, and the recommended Phase 2 dose (RP2D) of QL1706 in patients that have advanced malignant tumors. Result: The trial is ongoing. By December 2020, 47 patients with solid tumors were enrolled, 16 patients in dose-escalation and 31 patients in expansion cohorts, respectively. Nineteen (40.4%) patients had previous immunotherapy, and the median lines of previous systemic therapy were 2 (0-5). QL1706 demonstrated a well-tolerated safety profile in the doses from 0.3 to 5 mg/kg. Two patients at 10 mg/kg experienced a dose-limiting toxicity, respectively. Due to the unique design, the clearance rate of anti-CTLA-4 antibody was faster than that of anti-PD-1 component of QL1706 in all dosage groups, and the elimination half-lives (t1/2) of anti-CTLA-4 antibody and anti-PD-1 component following single-dose administration were 4~5 days and 6~9 days, respectively. As a result, a much-reduced level of exposure was achieved for the anti-CTLA-4 antibody compared to the anti-PD-1 antibody. This unique feature may have contributed to the good overall safety profile of the product. Treatment related adverse events (TRAEs) occurred in 66.0% (31/47) of patients. Five (10.6%) patients in the 5 mg/kg and 10 mg/kg groups experienced grade 3 or higher TRAEs. The most common (≥10%) TRAEs were pruritus [23.4% (11/47)], rash [21.3% (10/47)], AST increased [14.9% (7/47)], fatigue [12.8% (6/47)], hyperthyroidism [10.6% (5/47)], and hypothyroidism [10.6% (5/47)]. Partial responses were observed in 10 out of 35 (28.6%) evaluated patients and the overall DCR was 48.6% (17/35) in the mixed population. The regime of 5 mg/kg q3w was recommended as the RP2D based on the overall assessment of tolerability, pharmacokinetics, and clinical activity. Significance: QL1706, a dual immune checkpoint pathways (PD-1 and CTLA-4) blockade product evaluated in this phase I dose-escalation and expansion study, showed an acceptable safety profile and early evidence of clinical activity in advanced solid malignancies. Citation Format: Li Zhang, Hongyun Zhao, Yuxiang Ma, Yan Huang, Yang Zhang, Xiaoli Wei, Yanhua Yang, Wei Yang, Furong Liu, Zhuan Lin, Jianing Li, Wenfeng Fang, Qianwen Liu, Benyan Zou, Kunlun Liao, Liuqun Liu. Development and preliminary clinical activity of QL1706 (PSB205), a combination of anti-PD1 and anti-CTLA-4 antibodies manufactured together as a single product [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT119.