Dynavax Technologies Corporation (NASDAQ:DVAX) announced the first presentation of findings from an ongoing Phase 1/2 study evaluating SD-101, Dynavax’s intratumoral TLR9 agonist, in combination with Keytruda ® (pembrolizumab), Merck’s anti-PD-1 treatment. Early results evaluating five patients with metastatic melanoma for efficacy and 16 patients for safety were reported. In patients naïve to anti-PD-1 treatment objective responses were observed in three out of four (75%) including one complete response (CR) and two partial responses (PR’s). One patient with progressive disease while receiving anti-PD-1 therapy was observed to have stable disease (SD). These data were presented in a poster session on Sunday at the European Society of Medical Oncology (ESMO) Annual Congress 2016 in Copenhagen, Denmark.
SD-101 in combination with pembrolizumab was well-tolerated. No dose-limiting toxicities of the combination were observed in any dose cohort, and a maximum tolerated dose (MTD) was not identified. No immune-related adverse events were reported, and the most common treatment-emergent adverse events were grade 1-2 flu-like symptoms, including fever, chills and myalgia consistent with the engagement of TLR9 and production of interferon alpha. The study also included biomarker assessments suggesting that treatment with SD-101 and pembrolizumab resulted in elevation of gene signatures consistent with an increase in immune cell types and multiple immune functions.
About MEL-01 (KEYNOTE-184)
The ongoing dose-escalation and expansion study of SD-101 in combination with pembrolizumab includes patients with histologically or cytologically confirmed unresectable Stage IIIc/IV melanoma. The primary endpoints of the trial are MTD and evaluation of the safety of intratumoral SD-101 in combination with pembrolizumab. In addition, the trial is evaluating response as assessed by the investigator according to RECIST v1.1, biomarker assessments and duration of response. Patients previously treated with anti-PD-1 and other immunotherapies are included.
SD-101 is Dynavax’s proprietary, second-generation, Toll-like Receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. SD-101 activates multiple anti-tumor activities of innate immune cells and activates plasmacytoid dendritic cells to stimulate T cells specific for antigens released from dying tumor cells. TLR9 agonists such as SD-101 enhance T and B cell responses and provide potent Type 1 interferon induction and maturation of plasmacytoid dendritic cells to antigen-presenting cells. SD-101 is being evaluated in several Phase 1/2 oncology studies to assess its preliminary safety and activity.
For information about SD-101 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.