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
Sharma MR, Carvajal RD, Hanna GJ, Kang YK, Lee J, Lee KW, Li BT, Moore KN, Pegram M, Rasco D, Spira A, Wang D, Weinberg BA, Alonso M, Fang L, Husain A, Kowanetz M, Perez EA, and Dumbrava EI. M. Ann Oncol 2021; 32:S1453-S1454.
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.