Date: 2017-03-06
Type of
information: Presentation of results at a congress
phase: 1b-2
Announcement: presentation of results at the International Congress on Targeted Anticancer Therapies
Company: Dynavax (USA - CA)
Product: SD-101 and Keytruda® (pembrolizumab)
Action
mechanism:
- Toll-like receptor 9 agonist/TLR9 agonist/immunotherapy product/monoclonal antibody/immune checkpoint inhibitor. SD-101 is a second-generation, Toll-like receptor 9 (TLR9) agonist CpG-C class oligodeoxynucleotide. SD-101 is being studied for its multiple anti-tumor activities in innate immune cells and activation of 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 safety and activity.
- Keytruda® (pembrolizumab) is an highly selective monoclonal anti-PD-1 antibody designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, pembrolizumab enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system.
Disease: metastatic melanoma
Therapeutic
area: Cancer - Oncology
Country: Australia, Germany, New Zealand, USA
Trial
details:
- The dose-escalation and expansion study of SD-101 in combination with Keytruda® 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 Keytruda®. In addition, the trial is investigating 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. (NCT02521870)
Latest
news:
- • On March 6, 2017, Dynavax announced the presentation of findings in patients with metastatic melanoma in the dose escalation phase of an ongoing Phase 1b/2 study investigating SD-101 in combination with Keytruda® (pembrolizumab). Results evaluating 17 patients for efficacy and 22 patients for safety were reported. In patients naïve to anti-PD-1 treatment, responses were observed in six out of seven patients, for an Overall Response Rate (ORR) of 86%. This includes two (29%) complete responses (CR) and four (57%) partial responses (PR). Target tumor shrinkage was observed in all 7 evaluable patients. In 10 patients with progressive disease who initiated Keytruda® anti-PD-1 monotherapy prior to enrollment, one PR was observed and five patients had stable disease (SD) while receiving Keytruda® and SD-101, with four of the 10 patients experiencing target tumor shrinkage. These data are being presented by Robert Janssen, M.D., chief medical officer for Dynavax, in an oral presentation at the International Congress on Targeted Anticancer Therapies which begins today in Paris, France.
- SD-101 in combination with Keytruda® generally 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. The most common treatment-emergent adverse events were injection site reactions and transient grade 1 to 2 flu-like symptoms, including fever, chills and myalgia that respond to over the counter medications such as acetaminophen. The study also includes biomarker assessments, suggesting that treatment with SD-101 and Keytruda® resulted in elevation of gene signatures consistent with an increase in Th1 immune cell types as well as an increase in immune cell infiltrates such as CD8+ T-cells in the tumor microenvironment.
Is
general: Yes
