A first-in-human dose finding study of camrelizumab in patients with advanced or metastatic cancer in Australia

Jason D. Lickliter, Hui K. Gan, Mark Voskoboynik, Surein Arulananda, Bo Gao, Adnan Nagrial, Peter Grimison, Michelle Harrison, Jianjun Zou, Lianshan Zhang, Stacey Luo, Michael Lahn, Howard Kallender, Andrea Mannucci, Catello Somma, Katherine Woods, Andreas Behren, Pablo Fernandez-Penas, Michael Millward, Tarek Meniawy

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1177-1189
Number of pages13
JournalDrug Design, Development and Therapy
Volume14
DOIs
Publication statusPublished - 1 Jan 2020
Externally publishedYes

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