Issues

Preclinical studies have suggested that TLR9 activation can enhance antitumor immunity, suggesting the potential for combination therapies using the TLR9 agonist SD-101. Ribas and colleagues assessed the safety and efficacy of SD-101 administered into peripheral metastatic lesions in combination with systemic anti–PD-1 therapy in 22 patients with advanced melanoma. The overall response rate was 78% among the 9 anti–PD-1 naïve patients and 15% among the 13 patients who had received prior anti–PD-1 therapy. Similarly, Frank and colleagues evaluated intratumoral SD-101 in combination with low-dose radiation in a phase I/II trial of 29 patients with untreated indolent lymphoma. Objective responses occurred in 28% of patients. Tumor reductions at nontreated sites occurred in 83% of patients. Collectively these trials indicate that SD-101 is safe and can be combined with anti–PD-1 therapy or low-dose radiation to produce systemic antitumor response in patients with melanoma or lymphoma, respectively. For details, please see the articles by Ribas and colleagues on page 1250 and Frank and colleagues on page 1258.