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
  • 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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