NEW YORK – Seattle-based Silverback Therapeutics on Wednesday announced that it had begun dosing patients in a Phase I clinical trial evaluating SBT6050, an agent comprising a TLR8 agonist conjugated to a HER2-directed monoclonal antibody.
The multicenter trial, which plans to enroll roughly 210 participants, will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of the agent as a treatment for patients with advanced HER2-expressing solid tumors.
"In preclinical studies, SBT6050 demonstrated a broad therapeutic window," Valerie Odegard, Silverback's chief scientific officer, added in a statement, "and this profile has enabled the selection of a first-in-human starting dose projected to be pharmacologically active."
Silverback has designed SBT6050 to activate human myeloid cells in tumors expressing moderate or high levels of HER2. Patients' tumors will be considered HER2-expressing if they have immunohistochemistry scores of 2+ or 3+.
By activating myeloid cells present in patients' HER2-expressing tumors, SBT6050 harnesses the innate immune system's anti-tumor response. TLR8 is expressed in myeloid cells present in tumors, which the TLR8 agonist component targets, helping the immune system recognize and attack tumors.
The potential to maximize anti-tumor immune responses in this way is particularly important when tumors lack T cells, Silverback's President and CEO Laura Shawver said in a statement, "because the majority of cancer patients, including those whose tumors express HER2, do not respond to checkpoint inhibitors."