1. A First-in-Human Dose Finding Study of Camrelizumab in Patients with Advanced or Metastatic Cancer in Australia
- Author
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Lickliter JD, Gan HK, Voskoboynik M, Arulananda S, Gao B, Nagrial A, Grimison P, Harrison M, Zou J, Zhang L, Luo S, Lahn M, Kallender H, Mannucci A, Somma C, Woods K, Behren A, Fernandez-Penas P, Millward M, and Meniawy T
- Subjects
pd-1 ,monoclonal antibody ,first-in-human dose study ,cancer ,reactive cutaneous capillary endothelial proliferation ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Jason D Lickliter, 1 Hui K Gan, 2–4 Mark Voskoboynik, 1, 5, 6 Surein Arulananda, 2–4 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 1Nucleus Network, Melbourne, Victoria, Australia; 2Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia; 3Olivia Newton-John Cancer Wellness and Research Centre, Austin Hospital, Melbourne, Victoria, Australia; 4Department of Medical Oncology, La Trobe University School of Cancer Medicine, Bundoora, Victoria, Australia; 5Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria, Australia; 6Department of Medical Oncology, Monash University, Central Clinical School, Alfred Campus, Melbourne, Victoria, Australia; 7Blacktown Cancer and Haematology Centre, Blacktown Hospital, University of Sydney, Sydney, New South Wales, Australia; 8Department of Medical Oncology, Chris O’Brien Life House, Camperdown, New South Wales, Australia; 9Jiangsu Hengrui Medicine Co. Ltd, Shanghai, People’s Republic of China; 10Incyte Biosciences International Sarl, Geneva, Switzerland; 11Incyte Corporation, Wilmington, Delaware, USA; 12Department of Dermatology, The University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia; 13Linear Clinical Research, Nedlands, Western Australia, AustraliaCorrespondence: Jason D LickliterNucleus Network, Level 5, Burnet Tower, 89 Commercial Road, Melbourne, Victoria, AustraliaTel +61 3 9076 8900Fax +61 3 9076 8911Email j.lickliter@nucleusnetwork.com.auPurpose: 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.Methods: 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.Results: 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).Conclusion: Camrelizumab has manageable toxicity and encouraging preliminary antitumor activity in advanced solid tumors in Australia.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02492789.Keywords: PD-1, monoclonal antibody, first-in-human dose study, cancer, reactive cutaneous capillary endothelial proliferation
- Published
- 2020