Abstract 599TiP
Background
BT8009 is a Bicycle® Toxin Conjugate (BTC) in which a Nectin-4 binding Bicycle (bicyclic peptide) is conjugated through an inert sarcosine spacer chain and a cleavable linker to the antimitotic toxin MMAE. Targeting Nectin-4 is an established effective therapeutic strategy in 3rd-line bladder cancer following the recent approval in the U.S. of enfortumab vedotin for bladder cancer patients after receiving chemotherapy and immune checkpoint therapy. Nectin-4 has been shown to be highly expressed in bladder, NSCLC, upper GI, pancreatic, ovarian and breast cancers. Overexpression of Nectin-4 in tumor tissue is a marker for poor prognosis. BT8009 is designed to have rapid tumor penetration, release, and prolonged retention of MMAE in tumor and short terminal plasma half-life to reduce exposure to tissues outside of tumor. BT8009 exhibited a satisfactory preclinical profile supporting the initiation of a FIH study to investigate safety and efficacy in indications with evidence of Nectin-4 expression.
Trial design
BT8009-100 is an open-label, multicenter Ph. I/II study of BT8009 as a monotherapy and in combination with Q2W nivolumab in patients with advanced solid tumors associated with Nectin-4 expression that have recurred after exhausting standard treatment options. The primary objectives of the monotherapy and combination Ph. I dose escalations are to assess safety/tolerability and establish the RP2D for the Ph. II expansion phase. The secondary objective of the Ph. I is to assess preliminary signs of anti-tumor activity. Clinical activity in the target patient population will be the primary objective of the Ph. II portion. Initial dose escalation cohorts utilize a single subject design, which converts to a 3+3 design for intermediate cohorts and ultimately to a Bayesian design to determine MTD/MAD and RP2D for BT8009 with and without nivolumab. Eligible patients must be naïve to Nectin-4 directed therapies, must have available tumor tissue and acceptable hematologic and organ function, subject to certain exclusions. Enrollment in the Ph. I portion is ongoing at sites in the U.S., with sites expected to open in the EU and UK.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Sarah Cannon Development Innovations.
Funding
BicycleTx Ltd.
Disclosure
M. Mckean: Research grant/Funding (institution): Epizyme; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): Jacobio Pharmaceuticals ; Research grant/Funding (institution): Moderna; Advisory/Consultancy, Research grant/Funding (institution): Regeneron Pharmaceuticals ; Research grant/Funding (institution): Tizona Therapeutics; Research grant/Funding (institution): TopAlliance Biosciences; Research grant/Funding (institution): Prelude Therapeutics ; Research grant/Funding (institution): Ascentage Pharma Group; Research grant/Funding (institution): IDEAYA Biosciences; Research grant/Funding (institution): Oncorus; Research grant/Funding (institution): Ikena Oncology; Advisory/Consultancy: ArrayBioPharma; Advisory/Consultancy: MedPage Today. J.C. Bendell: Advisory/Consultancy, All payments made to Institution: Cerulean; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Merck; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Merrimack; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Taiho Oncology; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Bristol-Myers Squibb; Advisory/Consultancy, All payments made to Institution: Continuum Clinical; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Novartis; Advisory/Consultancy, All payments made to Institution: Tanabe Research Laboratories; Advisory/Consultancy, All payments made to Institution: FORMA Therapeutics; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Arrys Therapeutics; Advisory/Consultancy, All payments made to Institution: Evelo Biosccience; Advisory/Consultancy, All payments made to Institution: Sanofi-Aventis; Research grant/Funding (institution), All payments made to Institution: AbbVie; Research grant/Funding (institution), All payments made to Institution: Stemcentrix; Research grant/Funding (institution), All payments made to Institution: ADC Therapeutics; Research grant/Funding (institution), All payments made to Institution: Agios; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Arcus Bioscience; Research grant/Funding (institution), All payments made to Institution: Array BioPharma; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: AstraZeneca; Research grant/Funding (institution), All payments made to Institution: Bayer; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: BeiGene; Research grant/Funding (institution), All payments made to Institution: Bellicum Phamaceuticals; Research grant/Funding (institution), All payments made to Institution: Bicycle Therapeutics; Research grant/Funding (institution), All payments made to Institution: Blueprint Medicine; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Boehringer Ingelheim; Research grant/Funding (institution), All payments made to Institution: Boston Biomedical; Research grant/Funding (institution), All payments made to Institution: CALGB; Research grant/Funding (institution), All payments made to Institution: Calithera Bioscience; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Celgene; Research grant/Funding (institution), All payments made to Institution: Cyteir Therapeutics; Research grant/Funding (institution), All payments made to Institution: CytomX; Research grant/Funding (institution), All payments made to Institution: eFFECTOR Therapeutics; Research grant/Funding (institution), All payments made to Institution: Eisai; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Lilly; Research grant/Funding (institution), All payments made to Institution: EMD Serono; Research grant/Funding (institution), All payments made to Institution: Evelo Bioscience; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Genetech/Roche; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Five Prime Therapeutics; Research grant/Funding (institution), All payments made to Institution: Forty Seven; Research grant/Funding (institution), All payments made to Institution: Foundation bio; Research grant/Funding (institution), All payments made to Institution: Gilead Science; Research grant/Funding (institution), All payments made to Institution: Gossamer Bio; Research grant/Funding (institution), All payments made to Institution: Incyte; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Innate Pharma; Research grant/Funding (institution), All payments made to Institution: MacroGenics; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: MedImmune; Research grant/Funding (institution), All payments made to Institution: Merus; Research grant/Funding (institution), All payments made to Institution: Millennium Pharamceuticals; Research grant/Funding (institution), All payments made to Institution: Morphotek; Research grant/Funding (institution), All payments made to Institution: NGM Biopharmaceuticals; Research grant/Funding (institution), All payments made to Institution: Novocure; Research grant/Funding (institution), All payments made to Institution: Oncologie; Research grant/Funding (institution), All All payments made to Institutionpayments made to Institution: OncoMed Pharmaceuticals; Research grant/Funding (institution), All payments made to Institution: Pieris Pharamceuticals; Research grant/Funding (institution), All payments made to Institution: Relay Therapeutics; Research grant/Funding (institution), All payments made to Institution: Revolution Medicine; Research grant/Funding (institution), All payments made to Institution: Rgenix; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Seattle Genetics; Research grant/Funding (institution), All payments made to Institution: Synthorx; Research grant/Funding (institution), All payments made to Institution: Tempest Therapeutics; Research grant/Funding (institution), All payments made to Institution: Takeda Pharmaceuticals; Research grant/Funding (institution), All payments made to Institution: TG Therapeutics; Research grant/Funding (institution), All payments made to Institution: TRACON Pharamceuticals; Research grant/Funding (institution), All payments made to Institution: Tyrogenex; Research grant/Funding (institution), All payments made to Institution: Unum Therapeutics; Research grant/Funding (institution), All payments made to Institution: Scholar Rock; Research grant/Funding (institution), All payments made to Institution: GSK; Research grant/Funding (institution), All payments made to Institution: LEAP; Advisory/Consultancy, Research grant/Funding (institution), All payments made to Institution: Daiichi Sankyo; Research grant/Funding (institution), All payments made to Institution: SynDevRex; Research grant/Funding (institution), All payments made to Institution: Ipsen; Research grant/Funding (institution), All payments made to Institution: Oncogenex; Research grant/Funding (institution), All payments made to Institution: MEI; Research grant/Funding (institution), All payments made to Institution: Blueprint; Research grant/Funding (institution), All payments made to Institution: Jacobio; Research grant/Funding (institution), All payments made to Institution: Prelude Oncology; Research grant/Funding (institution), All payments made to Institution: Acerta Pharma; Research grant/Funding (institution), All payments made to Institution: Zymeworks; Advisory/Consultancy, All payments made to Institution: Janssen; Advisory/Consultancy, All payments made to Institution: Moderna Therapeutics; Advisory/Consultancy, All payments made to Institution: Pfizer; Advisory/Consultancy, All payments made to Institution: Piper Biotech; Research grant/Funding (institution), All payments made to Institution: Samsung Bioepis; Advisory/Consultancy, All payments made to Institution: Toledo Pharmaceuticals; Advisory/Consultancy, All payments made to Institution: Audro Biothech. D.P. Petrylak: Advisory/Consultancy, Research grant/Funding (institution): Ada Cap (Advanced Accelerator Applications) ; Advisory/Consultancy: Amgen; Research grant/Funding (institution): Agensys Inc; Advisory/Consultancy, Research grant/Funding (institution): Astella; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Bicycle Therapeutics; Research grant/Funding (institution): BioXcel Therapuetics; Advisory/Consultancy: Boehringer Ingleheim; Advisory/Consultancy, Research grant/Funding (institution): Bristol Myers Squib; Advisory/Consultancy, Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Endocyte; Advisory/Consultancy: Excelixis; Research grant/Funding (institution): Genentech; Advisory/Consultancy: Incyte; Research grant/Funding (institution): Innocrin; Advisory/Consultancy: Jannsen; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Mirati; Advisory/Consultancy: Monopteros; Research grant/Funding (institution): Novartis; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Pharmacyclics; Research grant/Funding (institution): Progenics; Research grant/Funding (institution): Replimune; Advisory/Consultancy, Research grant/Funding (institution): Roche; Research grant/Funding (institution): Sanofi Aventis; Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy: Urogen; Shareholder/Stockholder/Stock options: Bellicum; Shareholder/Stockholder/Stock options: Tyme. T.B. Powles: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): BMS; Advisory/Consultancy, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Incyte; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Ipsen; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck/MSD; Advisory/Consultancy, Research grant/Funding (self): Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): Merck/Serono; Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy, Research grant/Funding (institution): Johnson and Johnson; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche. G.P. Sonpavde: Research grant/Funding (institution): Boehringer-Ingelheim; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Onyx-Amgen; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy: Genentech; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Advisory/Consultancy: Seattle Genetics/Astellas; Advisory/Consultancy: Clinical Care Options; Advisory/Consultancy, Research grant/Funding (institution): AstraZenca; Advisory/Consultancy: Uptodate; Advisory/Consultancy: Exelixis; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb (BMS); Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy: Amgen; Advisory/Consultancy: Eisai; Advisory/Consultancy: NCCN; Research grant/Funding (institution): Celgene; Speaker Bureau/Expert testimony: Physicians Education Resource; Speaker Bureau/Expert testimony: Onclive; Speaker Bureau/Expert testimony: Research to Practice; Advisory/Consultancy: Bavarian Nordic; Advisory/Consultancy: Debiopharm; Advisory/Consultancy: QED; Advisory/Consultancy: Bicycle Therapeutics; Advisory/Consultancy: Dava oncology; Advisory/Consultancy: EMD Serono. A. Dickson: Full/Part-time employment: Bicycle Therapeutics. M.G. Hennessy: Full/Part-time employment: Bicycle Therapeutics. P. Jeffrey: Full/Part-time employment: Bicycle Therapeutics. M. Rigby: Full/Part-time employment: Bicycle Therapeutics. T. West: Full/Part-time employment: Bicycle Therapeutics. All other authors have declared no conflicts of interest.