Background: Bolus cisplatin in combination with radiation therapy is a standard of care for the treatment of locally advanced SCCHN, but contraindications such as hearing loss, tinnitus, inadequate renal function or neuropathy are common. Pembrolizumab is a PD1 inhibitor with FDA approval for the treatment of platinum-refractory recurrent SCCHN. Methods: This is a phase II study (NCT02609503) for patients with locally advanced SCCHN who are not optimal candidates for the standard therapy of cisplatin and radiation. The primary endpoint is PFS. Patients are treated with 3 cycles of pembrolizumab concurrent with radiation followed by 3 adjuvant cycles. Planned accrual is 29 subjects and 18 patients have been accrued. Because of rapid advance in studies combining PD1-axis agents with radiotherapy, we report early toxicity data on the first 12 patients who have completed six cycles of pembrolizumab and at least 30 days of followup from last pembrolizumab dose. Results: All patients completed 70 Gy radiation. 11 patients completed 6 cycles of pembrolizumab and 1 patient completed 5 (discontinued due to PD, not toxicity). The most common primary reason for cisplatin ineligibility was abnormal hearing (4) followed by tinnitus (3), nephropathy (2), neuropathy (2) and diabetes with poor control (1). The most common toxicities were mucositis and lymphopenia. Pneumonitis and auto-immune toxicity were absent. All toxicities that occurred more than once and listed as possible, probable or definitely related to pembrolizumab and radiation are listed in the table. PEG tubes were placed in 3 patients. Conclusions: Early data suggest low toxicity and high feasibility of pembrolizumab combined with radiotherapy. Clinical trial information: NCT02609503