On June 2, 2017 Dynavax Technologies Corporation (NASDAQ: DVAX) reported the presentation of findings in patients with metastatic melanoma in the dose escalation phase of an ongoing Phase 1b/2 study investigating SD-101, Dynavax’s intratumoral TLR9 agonist, in combination with KEYTRUDA (pembrolizumab), an anti-PD-1 therapy developed by Merck, known as MSD outside the United States and Canada (Press release, Dynavax Technologies, JUN 2, 2017, View Source [SID1234519437]). Results evaluating 19 patients for efficacy and 22 patients for safety were presented in a poster at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago:

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• In 7 anti-PD-1/L1-naïve patients, SD-101 used in combination with KEYTRUDA resulted in an overall response rate (ORR) of 100%, with a complete response (CR) rate of 29%. This is a meaningful increase over use of KEYTRUDA alone, which has already shown a 33% ORR, with a 6% CR.1

• In 12 patients with advanced (stage IIIc/IV) melanoma who had previously failed on anti-PD-1 treatment, introduction of SD-101 resulted in tumor shrinkage in 42% of patients, with 17% having a partial response (PR), indicating an anti-tumor immune response generated by SD-101.

• The combination of SD-101 and KEYTRUDA in this study, mobilized both innate and adaptive immune response in study participants.

• Tumor shrinkage was observed in non-injected visceral lesions.

"Having 7 out of 7 patients naïve to anti-PD-1/L1 treatment responding is very encouraging," said Antoni Ribas, M.D., Ph.D., of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, and lead investigator. "These results are supported by tumor shrinkage in patients who had previously progressed on anti-PD-1 treatment and by confirmatory laboratory biomarker assessments in tumor biopsies. If these clinical results are sustained in the ongoing trial, this combination, which mobilizes both innate and adaptive immune responses in patients, could represent an important advancement in immuno-oncology."

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. The study also includes biomarker assessments, suggesting that treatment with SD-101 and KEYTRUDA resulted in increased tumor-infiltrating lymphocytes and decreased Th2 in tumor biopsies, consistent with induction of an antitumor immune response.

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About MEL-01 (KEYNOTE-184)
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.

About SD-101
SD-101 is Dynavax’s proprietary, 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.

For information about SD-101 trials that are currently recruiting patients, please visit www.clinicaltrials.gov.