A phase Ib study of JS001, a humanized IgG4 mAb against programmed death-1 (PD-1) combination with axitinib in patients with metastatic mucosal melanoma.

Abstract

9528 Background: There was no standard treatment for metastatic mucosal melanoma. Preclinical data showed that axitinib increases the infiltration of immune cells and reduces the suppressive capacity of monocytic MDSCs in an intracranial mouse melanoma model. JS001 is a humanized IgG4 mAb against programmed death-1 (PD-1) with clinical activity in metastasis melanoma.This study is a phase Ib dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of JS001 combination with axitinib in patients with metastatic mucosal melanoma. Methods: Eligibility criteria include: histologically confirmed metastatic mucosal melanoma, archival or fresh tumor biopsy, ECOG PS 0-1, no prior system treatment. The patients will receive JS001 (1mg/kg or 3 mg/kg IV Q2W) combined axitinib (5 mg BID) in dose-finding and dose-expansion parts and treatment will be given until confirmed disease progression, unacceptable toxicity, withdrawal, or study termination. After the MTD or the optimal biological dose is identified, an expansion cohort of 30 patients were enrolled to further characterize the safety and efficacy. Other objectives include pharmacokinetics, pharmacodynamics, immunogenicity and tumor tissue biomarkers. Results: Enrollment began in April 2017. The majority of melanomas is mucosal origin included esophagus, nasopharynx, rectal melanoma and vaginal melanoma. As of February 10, 2018, enrollment has been completed with 33 patients. No dose-limiting toxicities (DLTs) were reported during dose escalation. 30 patients were treated with JS001 (3 mg/kg) combined axitinib (5mg Bid). The most common treatment-related AEs were grade 1/2, including hypertension, hand-foot skin reaction, oral ulcer, hypo-thyroidism and fever. Among 24 evaluable patients, no patient have complete response, 12 patients have partial response, and 9 pts achieve stable disease, for an ORR of 50% and a DCR of 87.5%. 10 out of 12 PR pts still have ongoing response. Conclusions: JS001 combined with axitinib may benefit for patients with metastatic mucosal melanoma.we will report all results during 2018 asco annual meeting. Clinical trial information: NCT03086174.