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e21530Background: EZH2 aberrations have been described in divers cancer types. However, the status and the clinical significance of EZH2 copy number variation have not been investigated in Asian me...

9539Background: 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-...

9588Background: PD-1 checkpoint blockade immunotherapy induces long durable responses in patients with advanced melanoma. However, only a minor subset of acral melanoma patients could gain benefit ...

3067 Background: JS001 blocks the interaction between PD-1 and its ligands and eradicates established tumor in human PD-1 Knock-in mouse model. Methods: A Phase I open-label study is designed to evaluate the safety and tolerability of JS001 in advanced solid tumor pts who are refractory to standard therapy. The study has a 3+3 dose escalation design with planned cohorts at 1, 3, and 10 mg/kg followed by a dose expansion. (Clinical Trial ID: NCT02836795). Results: As of January 27, 2017, pts enrollment has been completed with 36 pts from 3 indications (22 Melanoma; 9 Urothelial Carcinoma; 5 Renal Cell Carcinoma). The majority of melanomas are acral and mucosal origin. No DLT was observed and no MTD was reached in the study. The most common treatment-related AEs were grade 1/2, including hyper- or hypo-thyroidism (42%), rash (39%), fever (28%), leukopenia (22%), elevation of liver enzymes (19%), anorexia (17%), and fatigue (14%). Treatment–related grade 3 AEs include proteinuria (n = 1), and lipase increase (n = 2). The emergence of AEs is not dose related. JS001 PK shows dose-dependent exposure with the elimination half-life of 6 to 12 days. Among 32 evaluable pts, 1 pt have complete response (melanoma), 6 pts have partial response (3 melanoma, 2 RCC and 1 UC), and 10 pts achieve stable disease, for an ORR of 22% and a DCR of 53%. 6 out of 7 CR/PR pts still have ongoing response. Two groups of pts benefited most from JS001 treatment, pts with high tumor-infiltrating lymphocytes (TIL) (50% ORR) and pts with > 1% PD-L1 expression in tumor biopsy (46% ORR). Conclusions: JS001 exhibited a favorable safety profile in human. Treatment related AEs are in line with those from approved drugs in the same class. JS001 has demonstrated promising anti-tumor activity, especially in previously under-evaluated acral (20% ORR, 53% DCR) and mucosal (25% ORR, 50% DCR) melanomas. Clinical trial information: NCT02836795.

e21055 Background: Assessment of PD-L1 expression in tumor biopsy has been widely used for predicting anti-PD-1 therapy. Several factors, including tumor heterogeneity, false negative staining and unavailability of biopsy samples limit the application. Natural killer (NK) cells exert cytotoxicity against cancer cells. Therefore, we explored using NK cells percentage in peripheral blood (PB) as a biomarker to identify pts who are more likely to benefit from anti-PD-1 therapy. Methods: Pts treated with anti-PD-1 antibody (JS001) 1 mg/kg, 3mg/kg or 10mg/kg every 2 weeks in a Phase I clinical trial (ClinicalTrials.gov Identifier: NCT02836795) had PB collected at baseline and at time of radiographic evaluation performed every 8 wks. Disease status (shrinking stable disease, growing stable disease, partial response, complete response, or progressive disease) was characterized using RECIST v1.1 and immune-related response criteria. Frequencies of NK cells (CD3-CD16+CD56+) were measured by flow cytometry. Results: Thirty-six patients were enrolled in this trial, including 22 melanoma, 9 urothelial carcinoma and 5 renal cell carcinoma. As of 1/27/2017, median treatment duration: 3.92 months. Radiographic tumor evaluation has been performed in 32 pts: 1/32 CR, 6/32 PR, 6/ 32 shrinking SD, 4/32 growing SD and 15/32 PD. Pts with high NK cells at baseline observed 60% (6/10) Clinical Benefit Rate (CR/PR/ shrinking SD) versus 40% (13/32) in overall pts. Patients with clinical benefit had higher frequency of NK cells at baseline compared to pts with radiographic growing SD and PD (mean 24.3% vs. 17.9%, P = 0.076). Furthermore, pts with NK cell level consistently above UN or increasing above UN during treatment are more likely to get clinical benefit than those under UN (7/10 vs 3/22, P = 0.013). Conclusions: Baseline high NK cells frequency may predict a favorable response to anti-PD-1 therapy, which provides a non-invasive way to monitor response to PD-1 blockade. These results are being validated in a phase II trial. Clinical trial information: NCT02836795.

9512Background: Therapeutics for metastatic acral melanoma have not been successfully established. This study aims to investigate gene aberrations of CDK4 pathway in acral melanoma and evaluate the...

e21070Background: High-dose interferon alfa-2b(IFN-α-2b) improves the survival of high-risk melanoma patients, especially acral melanoma patient. However, there is a significant number of patients fails to benefit from treatment because of the toxicities. In this study, we aimed to identify baseline peripheral blood biomarkers to predict the outcome of acral melanoma patients with adjuvant high-dose interferon treatment. Methods: Pretreatment full blood counts, CD4+CD25+ regulatory T cells (CD4+Tregs),CD8+CD28-regulatory T cells(CD8+Tregs), CD8+CD28+cytotoxic T lymphocyte(CTL),serum lactate dehydrogenase (LDH), and clinical date were assessed in 113acral melanoma patients. 76 patients treated with 4-week IFN-α-2b (15*106 U/m2d1–5/w*4w) and 37 patients treated with1-year IFN-α-2b (15*106 U/m2 d1–5/w*4w + 9*106 U tiw*48w). Relapse free survival (RFS) and overall survival (OS) were assessed using the Kaplan–Meier method, and multivariate Cox regression analysis were applied, adjusting for other prognostic fa...