Abstract 209P
Background
SBT6050 comprises a TLR8 agonist linker-payload conjugated to a HER2-directed antibody and is designed to activate myeloid cells in tumors expressing moderate to high levels of HER2. TLR8 agonism directly activates myeloid cells and secondarily activates NK and T cells, inducing a broad spectrum of anti-tumor immune mechanisms.
Methods
This FIH study is evaluating SBT6050 alone and in combination with pembrolizumab (NCT04460456). Patients have HER2-expressing or -amplified solid tumors with progression following therapies known to confer clinical benefit. Single-agent and pembrolizumab combination dose escalations (Parts 1 and 3) will be followed by expansion cohorts at the RP2D (Parts 2 and 4).
Results
As of 4 April 2021, 18 patients across 10 tumor types were treated at 4 dose levels (Part 1, n=14; Part 3, n=4). Dose levels of SBT6050 ranging from 0.15 mg/kg to 1.2 mg/kg were pharmacologically active as demonstrated by the induction of blood-based biomarkers associated with myeloid cell and NK or T cell activation. SBT6050 exposures up to 0.6 mg/kg increase greater than dose-proportionally, and linear thereafter, reflecting evidence of target saturation at 0.6 mg/kg. Furthermore, increases in IFNγ, a marker for NK and/or T cell activation, along with additional on-target biomarkers, plateaued at 0.6 mg/kg. The most frequent (>25%) related TEAEs were chills, diarrhea, fatigue, hypotension, injection site reaction, nausea, pyrexia, and vomiting. Dose levels >0.6 mg/kg were evaluated to assess the upper limits of the dose range; Grade 3 DLTs that resolved with supportive care were observed in Part 1 at 1.2 mg/kg Q2 weeks. In response-evaluable patients (N=14), best overall response was PR (n=1), SD (n=3), and PD (n=10).
Conclusions
Based on preliminary safety data, SBT6050 given alone or in combination with pembrolizumab has a manageable safety profile. Related TEAEs are consistent with immune activation. A single-agent dose of 0.6 mg/kg administered Q2 weeks had a tolerable safety profile, drug exposure that reflects evidence of target saturation, and pharmacodynamics indicative of myeloid, NK and T cell activation.
Clinical trial identification
NCT04460456.
Editorial acknowledgement
Legal entity responsible for the study
Silverback Therapeutics, Inc.
Funding
Silverback Therapeutics, Inc.
Disclosure
S.J. Klempner, M. Beeram, A. Chan, S. Loi, D. Oh, L.A. Emens, A. Patnaik, J.E. Kim, Y.H. Park, S.A. Piha-Paul: Financial Interests, Institutional, Funding: Silverback Therapeutics, Inc.; Financial Interests, Institutional, Advisory Role: Silverback Therapeutics, Inc. E. Hamilton: Financial Interests, Institutional, Funding: OncoMed; Financial Interests, Institutional, Funding: Genentech/Roche; Financial Interests, Institutional, Funding: Zymeworksks; Financial Interests, Institutional, Funding: Rgenix; Financial Interests, Institutional, Funding: ArQule; Financial Interests, Institutional, Funding: Clovis; Financial Interests, Institutional, Funding: Silverback Therapeutics, Inc.; Financial Interests, Institutional, Funding: Millennium; Financial Interests, Institutional, Funding: Acerta Pharma; Financial Interests, Institutional, Funding: Sermonix Pharmaceuticals; Financial Interests, Institutional, Funding: Torque; Financial Interests, Institutional, Funding: Black Diamond; Financial Interests, Institutional, Funding: Karyopharm; Financial Interests, Institutional, Funding: Infinity Pharmaceuticals; Financial Interests, Institutional, Funding: Curis; Financial Interests, Institutional, Funding: Syndax; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Immunomedics; Financial Interests, Institutional, Funding: FujiFilm; Financial Interests, Institutional, Funding: Taiho; Financial Interests, Institutional, Funding: Decipera; Financial Interests, Institutional, Funding: Fochon; Financial Interests, Institutional, Funding: MedImmune; Financial Interests, Institutional, Funding: Seagen; Financial Interests, Institutional, Funding: Puma Biotechnology; Financial Interests, Institutional, Funding: Compugen; Financial Interests, Institutional, Funding: TapImmune; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: H3 Biomedicine; Financial Interests, Institutional, Funding: Takeda; Financial Interests, Institutional, Funding: Merus; Financial Interests, Institutional, Funding: Regeneron; Financial Interests, Institutional, Funding: Arvinas; Financial Interests, Institutional, Funding: StemCentRx; Financial Interests, Institutional, Funding: Verastem; Financial Interests, Institutional, Funding: eFFECTOR Therapeutics; Financial Interests, Institutional, Funding: CytomX; Financial Interests, Institutional, Funding: Harpoon; Financial Interests, Institutional, Funding: Orinove; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: Tesaro; Financial Interests, Institutional, Funding: Macrogenics; Financial Interests, Institutional, Funding: EMD Serono; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Institutional, Funding: Syros; Financial Interests, Institutional, Funding: Sutro; Financial Interests, Institutional, Funding: G1 Therapeutics; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: PharmaMar; Financial Interests, Institutional, Funding: Olema; Financial Interests, Institutional, Funding: Polyphor; Financial Interests, Institutional, Funding: Immunogen; Financial Interests, Institutional, Funding: Plexxicon; Financial Interests, Institutional, Funding: Amgen; Financial Interests, Institutional, Funding: Akesobio Australia; Financial Interests, Institutional, Funding: Shattuck Labs; Financial Interests, Institutional, Advisory Role: Genentech/Roche; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role: Novartis; Financial Interests, Institutional, Advisory Role: Dantari; Financial Interests, Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Advisory Role: Merck; Financial Interests, Institutional, Advisory Role: Puma Biotechnology; Financial Interests, Institutional, Advisory Role: Silverback Therapeutics, Inc.; Financial Interests, Institutional, Advisory Role: CytomX; Financial Interests, Institutional, Advisory Role: Pfizer; Financial Interests, Institutional, Advisory Role: Mersana; Financial Interests, Institutional, Advisory Role: Black Diamond; Financial Interests, Institutional, Advisory Role: H3 Biomedicine; Financial Interests, Institutional, Advisory Role: Daichi Sankyo; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Arvinas; Financial Interests, Institutional, Advisory Role: Deciphera Pharmaceuticals; Financial Interests, Institutional, Advisory Role: Eisai; Financial Interests, Institutional, Advisory Role: Seagen. V. Odegard: Financial Interests, Personal, Full or part-time Employment: Silverback Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Silverback Therapeutics, Inc.; Financial Interests, Personal, Royalties: Silverback Therapeutics, Inc. S. Hamke, G. Jang, C. Jacquemont: Financial Interests, Personal, Full or part-time Employment: Silverback Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Silverback Therapeutics, Inc. N. Hunder: Financial Interests, Personal, Full or part-time Employment: Silverback Therapeutics, Inc.; Financial Interests, Personal, Stocks/Shares: Silverback Therapeutics, Inc.; Financial Interests, Personal, Advisory Role: Blaze Biosciences.