Study design

This is a single-center, phase 1, open-label, 2-part (part A dose-escalation and part B dose-expansion) study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor activity of JS001, administered via intravenous (IV) infusion on an every 2-week (Q2W) dosing schedule in adult subjects with advanced melanoma or urologic cancers refractory to standard therapy (Clinical Trial ID: {"type":"clinical-trial","attrs":{"text":"NCT02836795","term_id":"NCT02836795"}}NCT02836795). This phase I study was approved by Peking University Cancer Hospital institutional review board.

In part A, the study could enroll up to 18 subjects with advanced melanoma or urologic cancers that were immunotherapy-naïve (no prior exposure to immunotherapy such as but not limited to anti-CTLA-4, anti-PD-1, or anti-PD-L1 antibodies). The planned cohorts in part A were 1 mg/kg, 3 mg/kg, and 10 mg/kg Q2W. A minimum of 3 subjects were initially enrolled at each dose level. Sequential subjects in a cohort received a single 60-min IV infusion of JS001 and were evaluated for toxicity for 28 days. DLT was defined as a treatment-related grade 3 or above AE or laboratory abnormality occurring within 28 days after the first dose. Provided there was no DLT in the initial 3 subjects, escalation to the next cohort could occur. If a DLT did occur, that cohort would be expanded to a total of 6 subjects. After 28 days following the first dose, subjects continued to receive JS001 at the intended dose level Q2W, followed by radiologic evaluation every 8 weeks (Q8W). Responses were evaluated by investigators using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Immune-related Response Evaluation Criteria In Solid Tumors (irRECIST). Subjects with progressive disease or an intolerant toxicity were taken off the study. Patients who initially developed progressive disease per RECISTv1.1 were allowed to continue therapy if investigator considered patients were benefiting from the treatment per irRECIST.

Any dose-escalation cohort that did not exceed the maximum-tolerated dose (MTD) could be expanded up to a maximum of 12 subjects in part B for further evaluation of safety, PK, pharmacodynamics, and clinical activity. In part B, subjects received JS001 through IV infusion at either 1, 3, or 10 mg/kg per dose Q2W, followed by radiologic evaluation Q8W until disease progression, development of intolerable toxicity, or voluntary withdrawal from the study. AEs are reported as of July 31, 2018. The latest survival follow-up was provided by July 3, 2018.