164P 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

BackgroundBDC-1001 is a novel ISAC consisting of an investigational trastuzumab biosimilar chemically conjugated to TLR7/8 agonist with non-cleavable linker. BDC-1001 elicits myeloid activation and enhances antigen presentation leading antibody-mediated effector functions that promote T-cell durable adaptive immune response.MethodsA 4-part, phase 1/2 dose-escalation/expansion study was initiated evaluate ± PD-1 inhibitor in pts previously treated advanced/metastatic HER2-expressing (IHC2/3+) or amplified solid tumors (NCT04278144). Pts received IV 3+3 design. Primary objectives are safety, tolerability, dose-limiting toxicities (DLTs), determine recommended 2 dose (RP2D); secondary exploratory assess pharmacokinetics (PK), pharmacodynamics (PD), preliminary antitumor activity.ResultsFrom the completed monotherapy dose-escalation (Part 1) will be reported including PK, PD biomarker data. The initial subset enrolled include following cancer types: breast, biliary, cervical, colorectal, lung, gastroesophageal, salivary, urinary tract, endometrial. Preliminary results first 20 indicate appears well-tolerated. No DLTs have been observed, MTD has not reached. AEs deemed related were grade 1-2, infusion-related reactions one event decreased ejection fraction. Early evidence clinical activity observed pt partial response other stable disease. Increases plasma biomarkers associated cell (TNFa, CXCL10, MCP-1, MIP-1a) observed. treatment led increase infiltration pts. Updated translational data anticipated.ConclusionsIn this first-in-human study, well-tolerated early activity, anti-HER2 therapy. Dose escalation ongoing.Clinical trial identificationNCT04278144.Editorial acknowledgementEditorial assistance provided by Phillips Gilmore Oncology Communications.Legal entity responsible for studyBolt Biotherapeutics, Redwood City, CA.FundingBolt CA.DisclosureM.R. Sharma: Financial Interests, Personal, Stocks/Shares: Abbott Laboratories; AbbVie; Alexion Pharmaceuticals; Amgen; Biogen; Bristol Myers Squibb; Lilly; Medtronic; Merck; Pfizer; Regeneron; Institutional, Funding: Alexo Therapeutics; Alpine Immune Sciences; Arrys Ascentage Pharma; Astellas AstraZeneca; Bolt Biotherapeutics; Celgene; Compugen; Constellation Coordination CytomX eFFECTOR Epizyme; Exelixis; Forty Seven; Genmab; GlaxoSmithKline/Tesaro; Helsinn Ikena Oncology; InhibRx; Innovent Biologics; Jounce KLUS PureTech; Sapience Seagen; Shattuck Labs; Symphogen; Syros Tempest Treadwell Therapeutics. R.D. Carvajal: Advisory Role: Aura Biosciences; Squibb/Medarex; Castle Chimeron Bio; Corvus Genzyme; Ideya; Immunocore; InxMed; Iovance Mirati Novartis; Oncosec; Pierre Fabre; Plexxikon; Rgenix; Roche/Genentech; Sorrento TriSalus Life Speaker’s Bureau: Array BioPharma; Bayer; Bellicum IDEAYA Incyte; Macrogenics; Roche/Genentech. G.J. Hanna: Other, Honoraria: Society Immunotherapy Cancer; Bicara Bio-Rad; Exicure; Kura Maverick Naveris; Prelude Conquer Cancer, ASCO Foundation; Elevar EMD Serono; Gateway Cancer Research; GlaxoSmithKline; Kartos Kite/Gilead; NantKwest; V Expert Testimony: Aaronson Rappaport Feinstein & Deutsch; Travel, Accommodations, Expenses: Regeneron. B.T. Li: Daiichi Sankyo; GRAIL; Guardant Health; Hengrui MORE Royalties: Karger Publishers - Book royalty; Shanghai Jiao Tong University Press Patents: US62/514,661; US62/685,057; Jiangsu Medicine; Health. K.N. Moore: Physicans' Education Resource; prIME Research To Practice; Aravive; Eisai; Genentech/Roche; Immunogen; Mersana; Myriad Genetics; Pfizer/EMD TESARO; Vavotar VBL AbbVie/Stemcentrx; Advaxis; Agenus; Clovis Genentech; Lilly Funding, Communication Inc: Invited Speaker: Novartis Pharmaceuticals UK Ltd.; Novogen; PTC Stem CentRx; Takeda; Tesaro; Verastem. M. Pegram: Seattle Genetics. D. Rasco: Asana Astex Boehringer Ingelheim; Gossamer Seven Eight Biopharmaceuticals; Takeda. A. Spira: Ownership Interest: AstraZeneca/MedImmune; Janssen Gritstone incyte; Jazz ADC Arch Ignyta; LAM Loxo; MedImmune; Newlink Roche; Rubius Trovagene. B.A. Weinberg: Onclive; Rafael Tempus; HalioDx; Sirtex Medical; Taiho Pharmaceutical; Ipsen; Isofol Caris Sciences. Alonso: Full part-time Employment: Biotherapeutics. L. Fang: MyoKardia. Husain, Kowanetz, E.A. Perez: E.I. Dumbrava: All authors declared no conflicts interest. response. MethodsA activity. A ResultsFrom anticipated. From ConclusionsIn ongoing. In