Background: hPV19 is a novel inhibitory mAb against VEGF with unique binding site different from that of Bevacizumab. This phase 1 study aimed to determine its dose-limiting toxicity (DLT), maximum tolerated dose (MTD), safety and pharmacokinetics (PK) in patients with advanced solid tumors. Methods: This is a first-in-human study with a 3+3 design. Eligible patients received hPV19 on day 1 and were observed for DLTs for 21 days. Subsequent treatment was every 14 days until disease progression or toxicity. DLTs were defined as occurrence of grade 3 or above non-hematological or grade 4 hematological toxicities. Response was evaluated at week 8 and then every 8 weeks using RECIST criteria. Extension enrollment (n = 5) was planned at dose levels 2.5 mg/kg and 6 mg/kg. Results: From 08/23/2016 to 01/25/2018, 24 patients were enrolled (22 for toxicity study) to 6 dose levels: 0.3 mg/kg (n = 3), 1 mg/kg (n = 3), 2.5 mg/kg (n = 8), 4mg/kg (n = 3), 6mg/kg (n = 4) and 10mg/kg (n = 3, not included in PK or response assessment). The median age was 46.5 years old (range 29-70). No DLTs have been observed and MTD has not been reached. Common grade 3 toxicities were hypertension 22.7%, proteinuria 9%, and LFT abnormalities 9%. Common grade 1 or 2 toxicities were hypertension 13.6%, proteinuria 59%, epistaxis 22.7%, dysphonia 18.2%, LFT abnormality 59%, renal abnormality 27.3%, anemia 22.7%, leukopenia 18.2% and thrombocytopenia 18.2%. A linear AUC dose response with elimination mean serum half-life (t_1/2) of 66.88-156.09h (2.78-6.50 days) and C_max of 4.06 to 132.01μg/ml were observed between doses 0.3 mg/kg to 6 mg/kg. Low titres of anti-hPV19 antibody were detected in 3 patients at 0.3 mg/kg (n = 1) and 1 mg/kg (n = 2). Six patients (27.2%) had clinical response, including 1 PR (breast ca, 2.5mg/kg), and 5 SDs (colon ca x2, renal ca x2 and breast ca x1, at all dose levels).　The median duration of response was 27 weeks (range 17-57 weeks). Conclusions: hPV19 is safe and tolerable with promising durable single agent activity in refractory solid tumors. The dose selected for phase Ib /phase II is 4 mg/kg every 2 weeks or 6 mg/kg every 3 weeks. Clinical trial information: CTR20160585.