SD-101 in Combination with Pembrolizumab in Advanced Melanoma: Results of a Phase Ib, Multicenter Study

Antoni Ribas, Theresa Medina, Shivaani Kummar, Asim Amin, Anusha Kalbasi, Joseph J. Drabick, Minal Barve, Gregory A. Daniels, Deborah J. Wong, Emmett V. Schmidt, Albert F. Candia, Robert L. Coffman, Abraham C.F. Leung, Robert S. Janssen

PD-1 inhibitors are approved for treating advanced melanoma, but resistance has been observed. This phase 1b trial evaluated intratumoral SD-101, a synthetic CpG-oligonucleotide that stimulates Toll-like receptor 9 (TLR9), in combination with pembrolizumab in patients with unresectable or metastatic malignant melanoma. The most common adverse events related to SD-101 were injection site reactions and transient, mild-to-moderate "flu-like" symptoms. Among the 9 patients naïve to anti-PD-1 therapy, the overall response rate (ORR) was 78%. The estimated 12 month progression free survival (PFS) rate was 88%, and overall survival (OS) rate was 89%. Among 13 patients having prior anti-PD-1 therapy, the ORR was 15%. RNA profiling of tumor biopsies demonstrated increased CD8+ T cells, NK cells, cytotoxic cells, dendritic cells, and B cells. The combination of intratumoral SD-101 and pembrolizumab was well tolerated and induced broad immune activation in the tumor microenvironment with durable tumor responses in both peripheral and visceral lesions.