Jason D Lickliter 1 , Hui K Gan 2 , 3 , 4 , Mark Voskoboynik 1 , 5 , 6 , Surein Arulananda 2 , 3 , 4 , Bo Gao 7 , Adnan Nagrial 7 , Peter Grimison 8 , Michelle Harrison 8 , Jianjun Zou 9 , Lianshan Zhang 9 , Stacey Luo 9 , Michael Lahn 10 , Howard Kallender 11 , Andrea Mannucci 10 , Catello Somma 10 , Katherine Woods 3 , Andreas Behren 3 , 4 , Pablo Fernandez-Penas 12 , Michael Millward 13 , Tarek Meniawy 13
18 March 2020
Camrelizumab inhibits PD-1 in non-clinical models and showed typical non-clinical pharmacokinetic (PK) and safety profiles for an IgG4 monoclonal antibody. We report results from the First-in-Human Phase 1 trial of camrelizumab in Australian population.
Camrelizumab was administered to patients with advanced solid tumors who had failed standard therapies. In the dose-escalation phase (n=23), camrelizumab was administered intravenously at 1 mg/kg, 3 mg/kg, 6 mg/kg, and 10 mg/kg every 2 weeks. In dose expansion (n=26), camrelizumab was given at 200 mg or 600 mg every 4 weeks.
Two dose-limiting toxicities were observed during dose escalation: transaminase elevation and diarrhea (both grade 3). Overall, treatment-related adverse events were consistent with the expected toxicity profile of immune checkpoint inhibition, with the striking exception of the dose-related development of angiomatous skin lesions characterized as reactive cutaneous capillary endothelial proliferation. The PK profile showed a dose-progressive increase in half-life from 3 days at 1 mg/kg to 7 days at 10 mg/kg. Moreover, receptor occupancy assays showed a PD-1 occupancy of >50% in most patients out to 28 days post-dose. The objective response rate was 15.2% (95% CI 6.3–28.9).
Camrelizumab has manageable toxicity and encouraging preliminary antitumor activity in advanced solid tumors in Australia.