Phase I safety and pharmacokinetic study of KN035, the first subcutaneously administered, novel fusion anti-PD-L1 antibody in Japanese patients with advanced solid tumors.

2609 Background: KN035 is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc, formulated for subcutaneous (SC) injection. A phase I safety and pharmacokinetic (PK) study was conducted in Japanese patients. Methods: Patients with advanced solid tumors were treated with KN035 SC once every-7-days (QW) or once every-14-days (Q2W) schedules with the dose limiting toxicities (DLT) evaluation period of 28 days. For the QW schedule, the starting dose was 1 mg/kg (n=3) with escalations to 2.5 (n=4), and 5 (n=3) mg/kg. For the Q2W schedule, 6 patients were planned at the dose levels of 2.5 and 5 mg/kg. Results: No DLT was observed up to the highest dose level of 5 mg/kg QW. No maximum tolerated dose (MTD) was reached. Among evaluable treated subjects (n=14), there were two confirmed partial responses. Preliminary PK analysis suggested that after SC administration, KN035 was slowly absorbed (Tmax ∼ 4 d) and the mean residual time (MRT) was 21 days. Apparent clearance (CL/F) and volume of distribution (Vz/F) were on average 0.58 L/day and 11 L, respectively. Plasma levels generally decreased mono-exponentially with an average terminal elimination half time around 13 days after reaching the peak concentration post SC administration. Exposures of KN035 increased approximately proportionally with dose. Trough concentrations were maintained above 15 µg/mL post administration of 5 mg/kg Q2W. No apparent exposure-body weight relationship was observed. Conclusions: KN035 exhibits a favorable safety profile in patients with advanced malignancies and preliminary results demonstrate encouraging anti-tumor activity. Based on PK data from the Q2W schedule, a fixed dose with less frequent dosing schedule of every 3 or 4 weeks is presently being evaluated. Clinical trial information: NCT03248843.