A phase II study of JS001, a humanized PD-1 mAb, in patients with advanced melanoma in China.

9539 Background: JS001, a humanized IgG4 antibody specific for human PD-1, has demonstrated favorable safety profile and promising anti-tumor activity in phase I clinical trial. Methods: This multi-center, open-label, phase II registration study is designed to evaluate safety and efficacy of JS001 in advanced melanoma patients who have failed systemic treatment. JS001 is given at 3 mg/kg IV Q2W until disease progression or intolerable toxicity. (Clinical Trial ID: NCT03013101). Results: Enrollment was completed by 9/15/2017 with 128 melanoma subjects enrolled (51 acral, 21 mucosal, 18 chronically sun-damaged (CSD), and 38 Non-CSD or origin unknown). As of 1/4/2018, among 121 evaluable subjects, all had at least two evaluations per RECIST1.1 by independent radiologic review committee. 1 CR, 24 PR and 48 SD were observed for an ORR at 20.7% and a DCR at 60.3%. ORR was lower in acral (14.3%) and mucosal (0%) subtypes when compared with CSD (35.3%) and non-CSD (33.3%). Nevertheless, significant DCRs were achieved in acral (53.1%) and mucosal (42.1%) melanoma subjects. Additional factors have been analyzed for correlation with clinical responses (Table 1). Median duration of response has not been reached, as most responses (23/25) are ongoing. There is no treatment related death in the study. The most common treatment related AEs were grade 1/2, including proteinuria (25%), ALT increase (25%), rash (22%), hyperglycemia (20%), amylase increase (18%), leukopenia (17%), anemia (16%), vitiligo (16%), AST increase (16%), pruritus (14%) and hypothyroidism (13%). Treatment related grade 3/4 AEs occurred in 18% subjects. Conclusions: This is the first reported large scale prospective anti-PD-1 clinical study in advanced melanoma subjects with an emphasis on acral and mucosal subtypes. Anti-PD-1 mAb appears more efficacious for CSD and non-CSD than acral and mucosal subgroups. Patients will be continuously monitored for safety and efficacy readouts (DOR, PFS and OS). Clinical trial information: NCT03013101.Clinical response analysis in subgroups. Group Value n ORR % ECOG 0 70 20.0 1 51 21.6 Prior lines of systemic therapy 1L 38 29.0 2L 28 25.0 3L 26 11.5 ≥4L 29 13.8 PD-L1 (≥1% cutoff with SP142) Positive 24 45.8 Negative 80 15.0 LDH (U/L) ≤ 280 104 21.2 > 280 17 17.7 Total 121 20.7