A Phase I Study Of Js001, A Humanized Pd-1mabin Patients With Advanced Triple Negative Breast Cancer.

e15093 Background: Triple negative breast cancer (TNBC), as defined by ER, PR and HER2 negative expression in tumor,has limited treatment options beyond traditional chemotherapy.Immunotherapy is a new breakthrough in advancedTNBC.JS001,a humanized IgG4 antibody specific for human PD-1, has demonstrated acceptable safety profile and preliminary anti-tumor activity in other solid tumors. Methods: This Phase I open-labelstudy is designed to evaluate safety and tolerability of JS001 in advanced TNBC patients who are refractory to systemic therapy. The study has a 3+3 dose escalation design with planned cohorts at 1, 3, and 10 mg/kg Q2W followed by a dose expansion. (Clinical Trial ID: NCT02838823). Results: From August 04,2016 to October 26, 2017,20 heavily-treated advanced TNBC patients were enrolled into three dose cohorts (6 in 1 mg/kg, 8 in 3 mg/kg and 6 in 10 mg/kg) with median age of 49. Median systemic lines of treatment received prior to JS001 is 4. All patients have been treated with taxanes and 18 patients (90%) have prior platinum-based chemotherapy.75% patients have metastasis in internal organs with poor prognosis. As of Jan 30, 2018, No DLT was observed and no MTD was reached in the study. The most common treatment related AEs were all grade 1/2,including hypo-(25%) or hyper- (15%) thyroidism, AST increase (20%), ALT increase (20%), anemia (20%), hyperglycemia (15%),hypertriglyceridemia(15%), pruritus (10%), and fatigue (10%).Treatment related grade 3 AEs include1 rash and 1 bronchospasm. The emergence of AEs is not dose related.Among 20 evaluable subjects, no patients obtained CR or PR, while 7 patients achieved stable disease,for a disease control rate (DCR)of 35%. 4 patients had stable disease over 6 months, with the longest at 8 months and still ongoing.50% subjects are PD-L1 positive (≥1% cutoff) in tumor biopsy, among whom a 40% DCR was observed. Conclusions: JS001 exhibited a favorable safety profile in advanced TNBC patients.Treatment related AEs are in line with approved drugs in the same class and no additional safety signal was observed.Combination of JS001 with traditional chemotherapy and/or anti-angiogenesis therapy are being evaluated for future clinical development in advanced TNBC patients. Clinical trial information: NCT02838823.