In an ongoing phase 1b dose escalation study, 22 patients with stage IIIC/IV metastatic melanoma were treated with intratumoral SD-101 (a CpG-oligonucleotide that stimulates TLR9) in combination with systemic pembrolizumab. Most adverse events were grade 1 or 2 and transient. In the 9 anti-PD-1/PD-L1 naive patients, ORR was 78% (2 patients with CR, 5 with PR), with both injected and non-injected lesions responding. Out of the 13 patients previously treated with anti-PD-1/PD-L1, 2 patients had a PR, and the rest went on to develop progressive disease. The treatment increased IFNα responses and infiltration of CD8+ T cells into the tumor.
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 naive 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.
Author Info: (1) Department of Medicine, University of California Los Angeles aribas@mednet.ucla.edu. (2) Department of Medicine/Medical Oncology, University of Colorado Comprehensive Cancer Ce
Author Info: (1) Department of Medicine, University of California Los Angeles aribas@mednet.ucla.edu. (2) Department of Medicine/Medical Oncology, University of Colorado Comprehensive Cancer Center. (3) Division of Oncology, Stanford University School of Medicine. (4) Levine Cancer Institute, Carolinas HealthCare System. (5) Department of Radiation Oncology, University of California Los Angeles. (6) Division of Hematology-Oncology, Milton S. Hershey Medical Center, Penn State Cancer Institute. (7) Mary Crowley Cancer Research Center. (8) Center for Personalized Cancer Therapy, and Division of Hematology and Oncology, UC San Diego Moores Cancer Center. (9) Department of Medicine, University of California Los Angeles. (10) Merck Research Laboratories. (11) Dynavax Technologies Corporation. (12) Dynavax Technologies Corporation. (13) Dynavax Technologies Corporation. (14) Dynavax Technologies Corporation.
