On September 16, 2021 Silverback Therapeutics, Inc. (Nasdaq: SBTX) ("Silverback"), a clinical-stage biopharmaceutical company leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered, tissue targeted therapeutics for the treatment of cancer, chronic viral infections, and other serious diseases, reported that interim clinical results from a Phase 1/1b clinical study of SBT6050 as a monotherapy and in combination with pembrolizumab in patients with advanced or metastatic HER2-expressing or amplified solid tumors, at the 2021 European Society for Medical Oncology Congress (Press release, Silverback Therapeutics, SEP 16, 2021, View Source [SID1234587838]).
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"Over this past year, we have gathered compelling data with clear signals of SBT6050’s pharmacological activity, marked by the activation of both the innate and adaptive immune response in patients," said Laura Shawver, Ph.D., chief executive officer of Silverback. "We look forward to moving into expansion cohorts and to expanding our clinical development plan to include combination with standard-of-care trastuzumab-containing regimens."
As of August 1, 2021, 40 patients with advanced or metastatic HER2-expressing or amplified solid tumors were enrolled into the SBT6050-101 trial. SBT6050 dose levels ranged from 0.3 to 1.2 mg/kg in the monotherapy dose escalation arm (Part 1), and 0.15 and 0.3 mg/kg in the pembrolizumab combination arm (Part 3). Patients received between 1 and 17 doses of SBT6050.
As a monotherapy and in combination with pembrolizumab, SBT6050 was generally well-tolerated, with an adverse event profile that is consistent with immune system activation and considered on-mechanism. "The adverse event profile thus far has been very manageable and importantly, suggests the potential to combine with other standard of care agents," said Samuel Klempner, MD, Medical Oncologist at the Massachusetts General Hospital. "The signals of anti-tumor activity are encouraging and its complementary mechanism of action with standard-of-care agents makes SBT6050 attractive for combination regimens."
Initial Safety Data
The most frequent treatment-related adverse events were consistent with immune activation, and included injection site reactions, fever and chills, hypotension, nausea, vomiting, and fatigue. These were mostly Grade 1 or 2 in nature, and no Grade 4 or higher related adverse events were reported.
At higher dose levels, dose limiting toxicities (DLTs) were observed and included Grade 3 hypotension, injection site reaction, fever, and hypoxia. These DLTs resolved with supportive care.
Cytokine release syndrome (CRS) > Grade 2 was not observed at any dose level.
Pharmacokinetic and Pharmacodynamic Data
SBT6050 exposures increased with dose and exhibited a linear PK profile at 0.6 mg/kg and higher. Linear exposure is evidence of saturation of receptor mediated clearance.
Conjugate stability was assessed using a highly sensitive assay, and no active levels of SBT6050’s free payload were detected in the blood and any amount of free payload was absent in 98% of all blood samples tested.
SBT6050 induces pharmacologic activity indicative of myeloid and NK/T cell activation at all dose levels, with effects plateauing at 0.6 mg/kg.
Pharmacodynamic activity is maintained with repeat dosing of SBT6050.
Anti-Tumor Activity
Early signals of anti-tumor activity were observed in a heavily pre-treated, heterogeneous population.
Among 18 evaluable patients for tumor types of interest, one patient with HER2 IHC 2+ NSCLC had a confirmed partial response (-55% per RECIST 1.1 criteria), maintained at the most recently available scan obtained at 36 weeks post-enrollment, and 8 weeks after discontinuing study treatment. In addition, stable disease was reported in seven patients.
SBT6050 targets the pertuzumab binding domain of HER2 and is designed to be used in combination with standard of care agents, including trastuzumab-containing regimens. Silverback will be discussing details of its expanded clinical development strategy on the scheduled investor webcast today.
Conference Call and Webcast on Thursday, September 16, 2021, at 6:30 AM ET
Silverback’s management team will host a conference call today at 6:30 AM ET. A live webcast, including slides, can be accessed through the Events section of the Company’s website at View Source An archived replay will be available shortly after the conclusion of the event.
About SBT6050
SBT6050 is the first of a new class of targeted immuno-oncology agents designed to direct a TLR8 agonist linker-payload to activate myeloid cells in tumors expressing moderate to high levels of HER2. TLR8 is expressed in myeloid cell types prevalent in human tumors and TLR8 agonism can activate a broad spectrum of anti-tumor immune mechanisms, including pathways involved in the innate and adaptive immune response. SBT6050 was specifically designed to bind to the HER2 sub-domain II, the pertuzumab epitope, to enable combinations with trastuzumab-containing therapies. SBT6050 is currently being evaluated in a Phase 1/1b trial in patients with advanced or metastatic HER2-expressing or amplified solid tumors.