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

Research output: Contribution to journalComment/debatepeer-review

210 Scopus citations


PD-1 inhibitors are approved for treating advanced melanoma, but resistance has been observed. This phase Ib 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 rate was 88%, and the overall survival 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, natural killer 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. SIGNIFICANCE: These early data demonstrate that the combination of pembrolizumab with intratumoral SD-101 is well tolerated and can induce immune activation at the tumor site. Combining an intratumoral TLR9 innate immune stimulant with PD-1 blockade can potentially increase clinical efficacy with minimal additional toxicity relative to PD-1 blockade alone.

Original languageEnglish (US)
JournalCancer Discovery
Issue number10
StatePublished - Oct 2018

All Science Journal Classification (ASJC) codes

  • Oncology


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