Intralesional SD-101 in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naive Head and Neck Squamous Cell Carcinoma: Results from a Multicenter, Phase II Trial

Purpose To determine whether SD-101, a Toll-like receptor 9 agonist, potentiates the antitumor activity of anti-PD-1 antibodies in patients with anti-PD-1/PD-L1 naive, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Patients and Methods: Patients with PD-1 Ab-naive HNSCC received either 2 mg SD-101 injected in one to four lesions or 8 mg SD-101 injected into a single lesion weekly x 4 doses then every 3 weeks x 7 doses. Pembrolizumab was administered at 200 mg every 3 weeks. Results: A total of 28 patients received 2 mg and 23 received 8 mg per injection, respectively. A total of 76% of patients had received prior systemic therapy. Combined positive score was >= 1 to < 20 in 35 patients (70%) and >= 20 in 15 patients (30%) of 50 patients with available data. There were 12 patients with grade >= 3 treatment-related adverse events (24%), and no treatment-related deaths. The objective response rate was 24% including 2 complete and 10 partial responses. The median duration of response was 7.0 [95% confidence interval (CI): 2.1-11.1] months. The response rate was higher in human papillomavirus-positive (HPV+) patients (44%, N = 16). Responses were not associated with PD-L1 expression levels or IFN gamma-related gene expression at baseline. Responses were observed both in injected (32%) and in noninjected lesions (29%). Progression-free and overall survival at 9 months were 19.0% (95% CI: 9.1-31.7) and 64.7% (95% CI: 45.3-78.7), respectively. Conclusions: SD-101 combined with pembrolizumab induced objective responses, especially in HPV+ tumors, which were frequently associated with increased intratumoral inflammation and effector immune cell activity.