TY - JOUR
T1 - A first-in-human dose finding study of camrelizumab in patients with advanced or metastatic cancer in Australia
AU - Lickliter, Jason D.
AU - Gan, Hui K.
AU - Voskoboynik, Mark
AU - Arulananda, Surein
AU - Gao, Bo
AU - Nagrial, Adnan
AU - Grimison, Peter
AU - Harrison, Michelle
AU - Zou, Jianjun
AU - Zhang, Lianshan
AU - Luo, Stacey
AU - Lahn, Michael
AU - Kallender, Howard
AU - Mannucci, Andrea
AU - Somma, Catello
AU - Woods, Katherine
AU - Behren, Andreas
AU - Fernandez-Penas, Pablo
AU - Millward, Michael
AU - Meniawy, Tarek
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Cancer
KW - First-in-human dose study
KW - Monoclonal antibody
KW - PD-1
KW - Reactive cutaneous capillary endothelial proliferation
UR - http://www.scopus.com/inward/record.url?scp=85082673981&partnerID=8YFLogxK
U2 - 10.2147/DDDT.S243787
DO - 10.2147/DDDT.S243787
M3 - Article
C2 - 32256049
AN - SCOPUS:85082673981
SN - 1177-8881
VL - 14
SP - 1177
EP - 1189
JO - Drug Design, Development and Therapy
JF - Drug Design, Development and Therapy
ER -
