DV281 is a novel investigational TLR9 agonist designed specifically for focused delivery to primary lung tumors and lung metastases. Clinical and preclinical studies with our more advanced cancer program, SD-101, have shown potential advantages of localized delivery of TLR9 agonists to the tumor site. DV281 is similar in biological activity and mechanism of action to SD-101, but has been optimized for delivery to lung cancer patients as an inhaled aerosol.
Studies in preclinical animal models of metastatic cancer show that direct delivery of DV281 to tumor-bearing lungs results in induction of interferons and cytokines and infiltration of T cells, responses similar to those observed after intratumoral injection of SD-101.
Cancer Res. 2018 Sep 1;78(17):4943-4956
Animal models also show that inhaled DV281 with anti-PD-1 antibodies can synergize to reduce tumor burden and generate a systemic and durable anti-tumor response. Inhibitors of the PD-1/PD-L1 pathway have become a standard treatment for patients with the most common form of lung cancer and Dynavax will focus clinical development on combinations of DV281 and a PD-1 inhibitor.
Clinical Studies with DV281:
Dynavax is currently conducting a Phase 1 clinical study in subjects with advanced non-small cell lung cancer to investigate the safety and tolerability of DV281 as monotherapy and in combination with an approved anti-PD-1 inhibitor (Nivolumab), and to identify a recommended dose for the expansion part of the study.
Title: Phase 1b Dose Escalation and Dose Expansion Trial of DV281 in Combination With an Approved Anti-PD-1 Inhibitor in Subjects With Advanced Non-Small Cell Lung Cancer