2. Academic Validation
  3. A First-in-Human Dose Finding Study of Camrelizumab in Patients with Advanced or Metastatic Cancer in Australia

A First-in-Human Dose Finding Study of Camrelizumab in Patients with Advanced or Metastatic Cancer in Australia

  • Drug Des Devel Ther. 2020 Mar 18;14:1177-1189. doi: 10.2147/DDDT.S243787.
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
Affiliations

Affiliations

  • 1 Nucleus Network, Melbourne, Victoria, Australia.
  • 2 Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia.
  • 3 Olivia Newton-John Cancer Wellness and Research Centre, Austin Hospital, Melbourne, Victoria, Australia.
  • 4 Department of Medical Oncology, La Trobe University School of Cancer Medicine, Bundoora, Victoria, Australia.
  • 5 Department of Medical Oncology, Alfred Hospital, Melbourne, Victoria, Australia.
  • 6 Department of Medical Oncology, Monash University, Central Clinical School, Alfred Campus, Melbourne, Victoria, Australia.
  • 7 Blacktown Cancer and Haematology Centre, Blacktown Hospital, University of Sydney, Sydney, New South Wales, Australia.
  • 8 Department of Medical Oncology, Chris O'Brien Life House, Camperdown, New South Wales, Australia.
  • 9 Jiangsu Hengrui Medicine Co. Ltd, Shanghai, People's Republic of China.
  • 10 Incyte Biosciences International Sarl, Geneva, Switzerland.
  • 11 Incyte Corporation, Wilmington, Delaware, USA.
  • 12 Department of Dermatology, The University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia.
  • 13 Linear Clinical Research, Nedlands, Western Australia, Australia.
PMID: 32256049 DOI: 10.2147/DDDT.S243787
Abstract

Purpose: 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; cancer; first-in-human dose study; monoclonal antibody; reactive cutaneous capillary endothelial proliferation.

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