Safety, activity, and pharmacokinetics of camrelizumab in advanced Asian melanoma patients: a phase I study

• Published in: BMC cancer 2022-05, Vol.22 (1), p.565-10, Article 565
• Main Authors: Zhou, Li, Wu, Xiaowen, Chi, Zhihong, Si, Lu, Sheng, Xinan, Kong, Yan, Mao, Lili, Lian, Bin, Tang, Bixia, Yan, Xieqiao, Wang, Xuan, Bai, Xue, Li, Siming, Wei, Xiaoting, Li, Juan, Yang, Qing, Guo, Jun, Cui, Chuanliang
• Format: Article
• Language: English
• Subjects: Advanced melanoma; Analysis; Anti-PD-1 antibody; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - pharmacokinetics; Antitumor agents; Apoptosis; Camrelizumab; Cancer therapies; Care and treatment; Cell death; Committees; Cytotoxicity; Diagnosis; Disease control; Dosage and administration; Drug dosages; Fever; Health aspects; Humans; Hyperthyroidism; Hypothyroidism; Immunoglobulin G; Immunotherapy; Inhibitor drugs; Medical treatment; Melanoma; Melanoma - drug therapy; Melanoma - pathology; Metastases; Metastasis; Monoclonal antibodies; Patient outcomes; Patients; PD-1 protein; Pharmacodynamics; Pharmacokinetics; Progression-Free Survival; Response rates; Risk factors; Safety; Software; Statistical analysis; Targeted cancer therapy; Triglycerides; Tumors; Vitiligo; γ-Glutamyltransferase
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-022-09663-5

Anti-programmed cell death receptor-1 (PD-1) monotherapy is the standard treatment for metastatic melanoma in current. Camrelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody whose safety and efficacy have not been reported in advanced Asian melanoma patients. This phase I study investigated the safety, activity, and pharmacokinetics of camrelizumab in Chinese patients with advanced melanoma. The study included two phases, the dose-escalation phase ("3 + 3" design at 60 mg, 200 mg, and 400 mg) and the dose-expansion phase. No dose-limiting toxicities were recorded over the dose-escalation phase, and the maximum tolerated dose was not reached. The most common treatment-related adverse events (TRAEs) in 36 patients were reactive cutaneous capillary endothelial proliferation, followed by rash, fever, hypothyroidism, hyperthyroidism, vitiligo, and fatigue. Five grade 3 or above TRAEs were reported (13.9%), including two cases of elevated γ-glutamyltransferase and blood triglycerides without clinical symptoms, and one liver injury recovered after symptomatic treatment. The confirmed overall response rate was 13.9% (95%CI: 4.7, 29.5%) and disease control rate was 38.9% (95%CI: 23.1, 56.5%). The median progression-free survival was 1.8 months (95%CI: 1.1, 2.4) and the median overall survival was 11.1 months (95%CI: 6.8, 15.4). Camrelizumab had acceptable tolerability and similar anti-tumor activity compared with other anti-PD-1 antibodies in advanced Asian melanoma patients. ClinicalTrials.gov identification: NCT02738489. Registered on 14/04/2016, prospectively registered.