Preliminary results from a phase I/II study of BDC-1001, a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), in patients (pts) with advanced HER2-expressing solid tumors

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Conference Proceeding

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Ann Oncol


Background: BDC-1001 is a novel ISAC consisting of an investigational trastuzumab biosimilar chemically conjugated to a TLR7/8 agonist with a non-cleavable linker. BDC1001 elicits myeloid activation and enhances antigen presentation leading to antibody-mediated effector functions that promote T-cell activation and a durable adaptive immune response.

Methods: A 4-part, phase 1/2 dose-escalation/expansion study was initiated to evaluate BDC-1001 PD-1 inhibitor in pts with previously treated advanced/metastatic HER2-expressing (IHC2/3+) or amplified solid tumors (NCT04278144). Pts received BDC-1001 IV in a 3+3 design. Primary objectives are to evaluate safety, tolerability, dose-limiting toxicities (DLTs), and determine a recommended phase 2 dose (RP2D); secondary and exploratory objectives are to assess pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity.

Results: From the completed monotherapy dose-escalation (Part 1) will be reported including safety, tolerability, PK, and PD biomarker data. The initial subset of pts enrolled include the following cancer types: breast, biliary, cervical, colorectal, lung, gastroesophageal, salivary, urinary tract, and endometrial. Preliminary results of the first 20 pts indicate that BDC-1001 appears well-tolerated. No DLTs have been observed, and the MTD has not been reached. AEs deemed related to BDC-1001 were grade 1-2, including infusion-related reactions and one event of decreased ejection fraction. Early evidence of clinical activity was observed in a pt with a partial response and other pts with stable disease. Increases in plasma biomarkers associated with TLR7/8 and myeloid cell activation (TNFa, CXCL10, MCP-1, MIP-1a) were observed. BDC-1001 treatment led to an increase in myeloid and T-cell infiltration in a subset of pts. Updated clinical and translational data are anticipated.

Conclusions: In this first-in-human study, BDC-1001 appears well-tolerated with early evidence of clinical activity, including pts previously treated with anti-HER2 therapy. Dose escalation is ongoing. Clinical trial identification: NCT04278144.





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