A Phase Ib Study Of Mk-3475 In Patients With Human Papillomavirus (Hpv)-Associated And Non-Hpv-Associated Head And Neck (H/N) Cancer

6011 Background: The PD-1 receptor-ligand pathway can be used by tumors to evade immune surveillance, thereby allowing neoplastic growth. MK-3475 is a highly selective, humanized IgG4/kappa isotype mAb designed to block PD-1 interaction with its ligands PD-L1 and PD-L2, to reactivate the immune system to eradicate the host tumor. Methods: Pts with recurrent/metastatic H/N cancer were enrolled in this multi-center, non-randomized trial in two cohorts (HPV and non-HPV associated). Pts were prescreened for PD-L1 expression by immunohistochemistry (22C3), and if positive allowed to proceed with treatment of single agent MK-3475 given intravenously at 10 mg/kg every 2 wks. Primary objectives are to determine (1) safety and tolerability and (2) anti-tumor activity of MK-3475 assessed by RECIST 1.1. Secondary objectives include progression-free survival, overall survival and response duration. Results: All results are based on preliminary, unaudited data as of Jan. 27, 2014. 77.9% of patients expressed PD-L1, defined as ≥1% of stained cells in the tumor microenvironment (Table). Of 60 patients (11 female, 49 male) enrolled in the study, 19 had an ECOG status of 0, and 40 had an ECOG status of 1 (1 unknown); 23 were HPV+ and 37 were HPV-; 9 had no prior systemic treatment, 10 had 1, 16 had 2, 13 had 3, and 7 had ≥4 prior regimens of treatment (5 unknown). Of the patients treated with MK-3475, 78.3% experienced ≥1 AE, and 46.7% reported a drug-related (DR) AE. The most common DR AEs reported were pruritis (6, 10%), fatigue (4, 7%), rash (4, 7%), and diarrhea (3, 5%). At least one Grade 3-5 AE was reported in 55.0% of patients, with 13.3% reporting a DR Gr 3-5 AE. Grade 3-5 AEs considered DR were hyponatremia, lymphopenia, rash, diarrhea, musculoskeletal pain, abscess (neck), and atrial fibrillation. Tumor shrinkage was observed in several patients, but protocol-specified efficacy analyses are not yet available. Conclusions: To date, treatment with MK-3475 has been well tolerated overall, with few serious DR AEs. Protocol-specified efficacy analyses are not yet available. Clinical trial information: NCT01848834.PD-L1 staining in tumors of screened patients (n=104). Staining (%) 0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 91-100 n 50 8 9 3 2 2 4 3 2 21