An open-label, multicenter, phase II study to evaluate the safety and efficacy of BB-1701, a novel antibody drug conjugate (ADC) targeting HER2, in previously treated patients (pts) with HER2+ or HER2-low unresectable or metastatic (M) breast cancer (BC)

BackgroundTreatment options for pts with unresectable/MBC have improved with targeted therapies such as trastuzumab deruxtecan (T-DXd), a HER2-directed ADC. Currently, there are limited treatment options for pts with HER2+/low MBC after treatment with T-DXd. BB-1701 is a HER2-directed ADC with eribulin (microtubule inhibitor) as a payload. Here we describe Study 205, an open-label, multicenter, phase 2 study of BB-1701 in pts with HER2+ or HER2-low unresectable/MBC who have previously received T-DXd.Trial designStudy 205 (NCT06188559) includes dose-optimization and dose-expansion parts for BB-1701. Eligible pts must have histologically confirmed HER2+ or HER2-low, unresectable or MBC, with measurable disease per RECIST v1.1. Prior treatment must include 1–3 prior chemotherapy-based regimens for unresectable/MBC, including T-DXd. The primary objectives of the dose-optimization part include determining the recommended dose (RD) and evaluating the safety/tolerability of BB-1701. The RD will be assessed by randomizing ∼50 pts into 1 of 3 dosing cohorts (1.6 mg/kg on day [D] 1 Q3W, 0.8 mg/kg on D1 and D8 Q3W, and 1.2 mg/kg on D1 Q3W; IV) in a 2:2:1 ratio. Randomization will be stratified by HER2 status (HER2+ vs. HER2 low) documented prior to T-DXd treatment. Dose expansion will enroll pts with HER2+ and/or HER2-low status at RD (n≈85 per cohort); the primary objective will evaluate the antitumor activity of BB-1701 at RD. In both study parts, secondary objectives include assessing additional efficacy measures (ie, DOR, PFS, OS, DCR, CBR) per RECIST v1.1 by the investigator (dose optimization) or by Blinded Independent Central Review (dose expansion). Adverse events will be recorded, monitored, and graded based on CTCAE v5.0. In both study parts, exploratory objectives will evaluate biomarkers expression and BB-1701 immunogenicity; other efficacy measures (ie, PFS on next-line of therapy) will be analyzed in the dose expansion only. As of April 30, 2024, 6 pts were screened; 4 have been randomized.Clinical trial identificationNCT06188559.Editorial acknowledgementMedical writing support was provided by Oxford PharmaGenesis Inc., Newtown, PA and was funded by Eisai Inc., Nutley, NJ, USA.Legal entity responsible for the studyEisai Inc., Nutley, NJ, USA.FundingEisai Inc., Nutley, NJ, USA.DisclosureM. George: Financial Interests, Personal, Advisory Board: Seattle Genetics, OBI Pharma; Financial Interests, Personal, Invited Speaker: Natera; Financial Interests, Institutional, Research Grant: Incyte, Oncolytics. J. Frenel: Financial Interests, Personal, Advisory Board: Pfizer, Novocure, Pierre Fabre, Eisai, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: GSK, Amgen, Eisai; Financial Interests, Institutional, Advisory Board: Exactscience, Lilly, Daiichi Sankyo, AstraZeneca, Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Novartis, MSD; Financial Interests, Coordinating PI: AstraZeneca, Seagen; Financial Interests, Local PI: MSD, Daiichi Sankyo; Non-Financial Interests, Principal Investigator: Novartis, Lilly, AstraZeneca, Pfizer, Daiichi Sankyo, MSD. J. Cortés: Financial Interests, Personal, Advisory Board, consulting/advisor: Roche, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Lilly, Merck Sharp & Dohme, Leuko, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies, Jazz Pharmaceuticals, Abbvie, Scorpion Therapeutics, Bridgebio, Biocon, Biontech; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Eisai, Pfizer, Lilly, Merck Sharp & Dohme, Daiichi Sankyo, AstraZeneca, Gilead, Steamline Therapeutics; Financial Interests, Personal, Stocks/Shares: MAJ3 Capital; Financial Interests, Personal, Stocks/Shares, (relative): Leuko; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Queen Mary University of London, Iqvia; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca, Steamline Therapeutics; Other, travel cost and expenses: Merck Sharp&Dhome. M. Schmidt: Financial Interests, Personal, Advisory Board: AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seagen, GILEAD, Stemline; Financial Interests, Institutional, Local PI: AstraZeneca, Roche, Novartis, Pierre Fabre; Financial Interests, Personal, Trial Chair: Pfizer. J. �. García Saenz: Financial Interests, Personal, Advisory Role: Seagen, AstraZeneca, Daiichi Sankyo, Novartis, Gilead, Menarini; Financial Interests, Personal, Other, Consultancy/speaker fees: Celgene, Eli Lilly, Eisai, MSD, Exact Sciences, Tecnofarma, Nolver (Adium), Asofarma, Roche; Financial Interests, Institutional, Research Funding: AstraZeneca; Financial Interests, Personal, Other, Travel support: Gilead, AstraZeneca, Daiichi Sankyo. S. Blau: Financial Interests, Personal, Advisory Role: IntegraConnect, Billion to One; Financial Interests, Personal, Leadership Role: Northwest Medical Specialties, Quality Cancer Care Alliance; Financial Interests, Personal, Expert Testimony: Northwest Medical Specialties; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Northwest Medical Specialties, Quality Cancer Care Alliance; Financial Interests, Personal, Stocks or ownership: Northwest Medical Specialties; Financial Interests, Personal, Other, Honoraria: Cardinal Health, Novartis, Puma Biotechnology, American Journal of Managed Care; Financial Interests, Personal, Research Funding: Northwest Medical Specialties. H. Sakai: Financial Interests, Personal, Invited Speaker, speaker honorarium: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eli Lilly, Chugai Pharmaceutical Co., Ltd, Gilead Sciences; Non-Financial Interests, Personal, Other, medical writing support: Daiichi Sankyo. S. Babu: Financial Interests, Personal, Leadership Role: Exigent Research; Financial Interests, Personal, Stocks or ownership: Fort Wayne Medical Oncology & Hematology; Financial Interests, Personal, Other, Honoraria: Janssen Scientific Affairs, Pfizer, Novartis, Cornerstone Healthcare Group; Financial Interests, Personal, Advisory Role: Cornerstone Specialty Network, E.R. Squibb Sons, LLC, Novartis, Kite, a Gilead company, Taiho Oncology; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, Novartis, Genentech/Roche, AstraZeneca/MedImmune, Janssen Oncology, Amgen, TG Therapeutics, AbbVie, Lilly, Alexion Pharmaceuticals, Merck, Novartis, Syndax, Nektar, Sanofi, Argenx, Gilead Sciences, BeiGene, Torl Biotherapeutics, 1200 Pharma, Takeda, Scholar Rock, Aptose Biosciences; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Kite, a Gilead company, Karyopharm, BeiGene, Janssen; Financial Interests, Other, Travel, Accommodations, Expenses: Pharmacyclics. N.P. McAndrew: Financial Interests, Personal, Advisory Board, US Medical Breast Cancer Steering Committee: AstraZeneca; Financial Interests, Personal, Advisory Board, Consulting: Novartis; Financial Interests, Personal, Writing Engagement, Consulting Retainer: GoodRx; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Novartis, Dizal Pharmaceuticals, Arvinas, Loxo, AstraZeneca, Seattle Genetics, Mersana. A. Ali: Financial Interests, Personal, Advisory Board: guardant, astrazeneca; Financial Interests, Personal, Invited Speaker: tarsera; Financial Interests, Institutional, Other, Research funding: tumorscope. M. Pavic: Financial Interests, Personal, Invited Speaker: Merck, Eisai, Janssen, Sanofi, Forus Therapeutics, GSK, EMD Serono; Financial Interests, Personal, Advisory Board: Janssen, Merck, Novartis, Forus Therapeutics. K. Jhaveri: Financial Interests, Personal, Advisory Role: Novartis, Pfizer, Taiho Oncology, Genentech, AbbVie, Eisai, AstraZeneca, Blueprint Medicine, Daiichi Sankyo, Sun Pharma Advanced Research Company Ltd, Menarini/Stemline, Gilead, Scorpion Therapeutics, Lilly/Loxo Oncology, Zymeworks; Financial Interests, Institutional, Research Funding: Novartis, Genentech, AstraZeneca, Pfizer, Lilly/Loxo Oncology, Zymeworks, Immunomedics/Gilead, PUMA Biotechnology, Merck Pharmaceuticals, Context Therapeutics, Scorpion Therapeutics, Blueprint Medicines. J.M. Jones: Financial Interests, Personal, Other, Travel, accomodations, expenses for investigator meeting: AstraZeneca. H.S. Rugo: Financial Interests, Personal, Advisory Board, Consultancy/advisory support: NAPO; Financial Interests, Personal, Invited Speaker, Honoraria: Mylan/Viatris, Chugai; Financial Interests, Personal, Advisory Board, Advisory/Consultancy: PUMA, Sanofi; Financial Interests, Institutional, Local PI: Novartis, Lilly, Pfizer, Daiichi, AstraZeneca, Gilead Sciences, Inc.; Financial Interests, Institutional, Coordinating PI: OBI Pharma, F. Hoffmann-La Roche AG/Genentech, Inc., Merck; Financial Interests, Institutional, Research Grant: Stemline Therapeutics, Ambryx. K. Mody: Financial Interests, Personal, Full or part-time Employment: Eisai. A.D. Smith: Financial Interests, Personal, Full or part-time Employment: Eisai. T. Yamashita: Financial Interests, Institutional, Speaker’s Bureau: Chugai, Eisai, Daiichi Sankyo, Taiho, Nippon Kayaku, AstraZeneca, Kyowa Kirin, Pfizer, Eli Lilly, Novartis Pharma, MSD; Financial Interests, Institutional, Research Funding: Chugai, Taiho, Nippon Kayaku, Eli Lilly, Daiichi Sankyo, Pfizer, AstraZeneca, Seagen, MSD, Kyowa Kirin, Ono, Gilead Sciences, Eisai. All other authors have declared no conflicts of interest.