988PDCLINICAL ACTIVITY AND SAFETY OF MEDI4736, AN ANTI-PD-L1 ANTIBODY, IN PATIENTS WITH HEAD AND NECK CANCER.

ABSTRACT Aim: Squamous cell carcinoma of the head and neck (SCCHN) is associated with tobacco use, human papillomavirus (HPV) infection, and PD-L1 expression. An ongoing Phase I, multicenter, open-label study (NCT01693562) is evaluating the safety and efficacy of MEDI4736, a human IgG1 mAb, engineered to prevent ADCC activity, that blocks PD-L1 binding to PD-1 and CD-80. Methods: MEDI4736 is administered IV every 2 weeks (q2w) at a dose of 10 mg/kg in a recurrent/metastatic SCCHN expansion cohort. Retreatment is permitted upon progression after 12 months of therapy. Smoking history, HPV status and prior treatments are collected at baseline. PD-L1 expression within the tumor is assessed by immunohistochemistry. Response is assessed by RECIST v1.1. Results: As of 14 Apr, 2014, 50 pts with SCCHN; mean age 58 y (range 24–96); 86% male, 63% current/prior smokers, with median 3 prior treatments (1–11), received median 3 doses (1–12) of MEDI4736 10 mg/kg q2w. Treatment-related adverse events (TRAE) were observed in 39% of pts; most frequently nausea (6%), diarrhea, dizziness, and rash (4% each). Dyspnea, syncope, raised gamma-glutamyltransferase (GGT) and sepsis (each 5%) were the most common grade ≥3 AEs; only raised GGT (n = 1) was considered treatment-related. No TRAEs led to study discontinuation and no pts had pneumonitis or colitis. Median time of follow up was 8 wks at data cutoff. In all, 29 SCCHN pts were evaluable for efficacy (first assessment at 6 weeks), with 7 having radiographic shrinkage in target tumor lesions ranging from 7% to 76%. Five of the 7 pts have been followed for at least 12 wks (6–24 wks) and none have evidence of objective progression. Four pts have a partial response (confirmed + unconfirmed). Further assessment of clinical activity and its potential relationship to clinical attributes (HPV status, smoking history, prior therapies), and biomarkers, including PD-L1 expression, are ongoing. Conclusions: Preliminary clinical activity in pts with SCCHN has been observed with manageable safety profile consistent with previous reports for MEDI4736. These data support continued clinical development of MEDI4736 in SCCHN. Disclosure: M. Fury: MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest. ; S.I. Ou: MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest. ; A. Balmanoukian: Our clinic, including myself, is involved with research/clinical trials funded by MedImmune. MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest. I have agreed to be a speaker for BI. ; A. Hansen: MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest. ; E. Massarelli: MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest. ; A. Blake-Haskins: Employee of MedImmune and owns stock/stock options in AstraZeneca X. Li: Employee of MedImmune and owns stock/stock options in AstraZeneca; P.B. Robbins: Employee of MedImmune and owns stock/stock options in AstraZeneca; J. Vasselli: Employee of MedImmune and owns stock/stock options in AstraZeneca; N.H. Segal: Ad Board participation with MedImmune, Alkermes Scientific, Imugene Research funding from BMS and Pfizer. MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest.