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

Abstract

Background 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. Methods 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. Results 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). Conclusions Camrelizumab had acceptable tolerability and similar anti-tumor activity compared with other anti-PD-1 antibodies in advanced Asian melanoma patients. Trial registration ClinicalTrials.gov identification: NCT02738489. Registered on 14/04/2016, prospectively registered.

Recent advances in immunotherapy and its combination therapies for advanced melanoma: a review

“…Similarly, camrelizumab showed preliminary anti-tumor activity in the first treatment of advanced solid tumor patients in Australia ( 18 ). Moreover, in the subsequent Phase I study on patients with advanced melanoma in Asia, the efficacy of camrelizumab was similar to that of toripalimab in the POLARIS-01 study, with objective response rates (ORRs) of 15.2% and 17.3%, respectively ( 19 , 20 ).…”

Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma

“…The dose of camrelizumab was selected based on a phase 1 trial of melanoma. 37 The dose of apatinib was selected according to the recommended dose when used in combination with camrelizumab in previous dose-escalation studies. 38,39 The dose of temozolomide was selected based on its previous phase 3 trials in melanoma.…”

“…Patients received intravenous camrelizumab, 200 mg, once every 2 weeks; oral apatinib, 250 mg, once daily; and intravenous temozolomide, 200 mg/m 2 , once daily on days 1 to 5 every 4-week cycle. The dose of camrelizumab was selected based on a phase 1 trial of melanoma . The dose of apatinib was selected according to the recommended dose when used in combination with camrelizumab in previous dose-escalation studies .…”

Experiences of immune-related skin toxicity: a qualitative study among patients with cancer

“…to a reduction or discontinuation of antitumor medications, affecting the progress of treatment [6][7][8]. Immune-related cutaneous adverse events are an early form of immune-related adverse events, which include pruritus, rash, and reactivity skin capillary endotheliosis, oral mucosal lichenoid reaction and Sjögren's syndrome, bullous pemphigoid, vitiligo, and Stevens-Johnson syndrome [8,9]. In one study, the incidence of immune-related cutaneous adverse events was 43-45% in patients treated with CTLA-4 inhibitors and approximately 18-23% in patients treated with PD-1 inhibitors [10].…”