Background: KN035 is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc fragment, formulated for subcutaneous (SC) injection. Methods: The escalation phase followed a modified 3+3 design with a 28-day DLT evaluation period and 8 dose levels were planned at 0.1, 0.3, 1.0, 2.5, 5 and 10 mg/kg SC weekly. One patient each was enrolled at 0.1 and 0.3 mg/kg dose levels. Additional dose levels followed traditional 3+3 design. Response was assessed per RECIST 1.1 every 12 weeks. Results: As of 11/2/2018, 17 patients were enrolled in the escalation phase (urothelial carcinoma (n=2), hepatic cell carcinoma (n=2), intrahepatic cholangiocarcinoma (n=2), thymic carcinoma (n=2), colorectal cancer£¨n=2£©£¬renal cell carcinoma (RCC, n=3), Squamous-cell lung carcinoma (n=1) and ovarian cancer (n=1)). The majority of subjects had advanced disease stage, stage IV (15/17) and stage III (2/17). A total of 7 subjects received radiotherapy, 16 subjects received surgery, and 13 subjects received systematic anti-cancer therapies from previous treatment. None had received prior checkpoint inhibitor treatment. Planned maximum dose of 10 mg/kg was reached (n=3) without DLT occurred. There was only one Grade 3 drug related Treatment Emergent Adverse Event (TEAE) occurred at 0.3 mg/kg dose level, which was immune related dermatitis and resolved later. All other drug related TEAEs were either Grade 1 or 2, with the most common events as elevated ALT (5/17) and elevated AST (4/17). Among all enrolled subjects, three subjects had confirmed PR, including one RCC subject at 2.5 mg/kg and one Intrahepatic cholangiocarcinoma subject at 5 mg/kg, and one cholangiocarcinoma subject at 10 mg/kg. Conclusions: KN035 exhibits a favorable safety profile and promising preliminary anti-tumor activity in patients with advanced malignancies. Clinical trial information: NCT03101488