652P - BT8009 monotherapy in enfortumab vedotin (EV)-naïve patients (pts) with metastatic urothelial carcinoma (mUC): Updated results of Duravelo-1

Background

BT8009 is a highly selective Bicycle® Toxin Conjugate targeting Nectin-4, which is overexpressed in mUC and other cancers. BT8009 has lower molecular weight and shorter plasma half-life than antibody drug conjugates, with potential to rapidly penetrate tumors and minimize healthy tissue exposure. The ongoing phase 1/2 study (NCT04561362) is evaluating BT8009 ± pembrolizumab in pts with advanced solid tumors associated with Nectin-4 expression. Updated results from BT8009 monotherapy at recommended phase 2 dose (RP2D) of 5 mg/m² weekly (QW) in EV-naïve pts with mUC are reported.

Methods

Eligible pts had unresectable mUC, creatinine clearance ≥50 mL/min, prior anti–PD-1/PD-L1 exposure, had progressed on or were ineligible for platinum-based chemotherapy, and had received no prior EV. All pts who received the RP2D of 5 mg/m² BT8009 monotherapy QW across dose escalation and expansion phases were included for analysis. Antitumor activity, safety, and pharmacokinetics (PK) data are summarized.

Results

In total, 45 pts with median age 67 years (range 42–84) and median 2.5 prior lines of therapy (range 1–7) were included. Median time on treatment was 16.1 weeks (1–101.4). Best overall response in 38 efficacy-evaluable pts, was 45% (n=17), including 1 confirmed complete response (3%) and 16 (13 confirmed) partial responses (42%). Stable disease (≥16 weeks) was maintained in 9 pts. Median duration of response was 11.1 months (95% CI 3.9, NR), among pts with confirmed responses (n=14). Safety is summarized in the table. There were no Grade ≥3 treatment-related adverse events of neuropathy (any kind), skin reactions, or eye disorders. The PK of EV-naïve pts with mUC was consistent with PK observed across the entire study.

Conclusions

This ongoing study of BT8009 monotherapy at 5 mg/m² QW shows a promising response profile and a generally well-tolerated safety profile in pts with mUC. A phase 2/3 study (NCT06225596; Duravelo-2) is currently enrolling. Table: 652P

*Contains data from dose escalation and dose expansion phases. EV, enfortumab vedotin; pts, patients; mUC, metastatic urothelial carcinoma; TEAE, treatment-emergent adverse event; TRAE, treatment-related adverse event.

Clinical trial identification

NCT04561362.

Editorial acknowledgement

Writing assistance was provided by Rebecca L. Crepeau, PhD of Fishawack Communications Ltd, part of Avalere Health.

Legal entity responsible for the study

BicycleTx Ltd.

Funding

BicycleTx Ltd.

Disclosure

O. Reig Torras: Financial Interests, Personal, Invited Speaker: Pfizer, BMS, Ipsen. L. Crouzet: Financial Interests, Personal and Institutional, Advisory Board: BMS; Financial Interests, Personal and Institutional, Invited Speaker: Janssen; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor: Astellas, Viatris. A. Necchi: Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Ipsen, BMS, Gilead; Financial Interests, Personal, Steering Committee Member: Roche, Janssen, Bayer, Astellas, AstraZeneca, Merck, Clovis Oncology; Financial Interests, Coordinating PI: Incyte; Financial Interests, Local PI: Pfizer; Non-Financial Interests, Leadership Role: Global society of Rare Genitourinary Tumors (GSRGT). C. Baldini: Financial Interests, Institutional, Advisory Board: BMS, MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Coordinating PI: iTeos, Janssen, Seattle Genetics, Taiho, Pyramid Bioscience; Financial Interests, Institutional, Local PI: AZ, Amgen, Bicycle Therapeutics, MSD, Tango, Roche Genentech; Non-Financial Interests, Member: ASCO, SIOG, SOFOG, AACR, ESMO. M.J. Lostes Bardaji: Non-Financial Interests, Advisory Board: SEOM, ESMO. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. L. Verlingue: Financial Interests, Personal, Stocks/Shares, CEO of Resolved dedicated to treatment approval prediction: Resolved; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Contract for bioinformatic analysis: Pierre Fabre, Servier; Non-Financial Interests, Advisory Role: Klineo; Non-Financial Interests, Institutional, Proprietary Information, As part of the Drug Development Department (DITEP) of Gustave Roussy and of the Phase 1 Unit of Centre Léon Bérard, as medical doctor: Principal/sub-Investigator of Clinical Trials for AbbVie, Adaptimmune, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co, Clovis Oncology, Cullinan-Apollo, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Tharapeutics, Gamamabs, Genentech, GSK, H3 Biomedicine, F. Hoffmann-La Roche Ag, Imcheck Therapeutics, Innate Pharma, Institut de Recherche Pierre Fabre, Iris Servier, Janssen Cilag, Janssen Research Foundation, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Lytix Biopharma A: Pharmas. V. Boni: Financial Interests, Personal, Advisory Board: EMD Serono, Janssen; Financial Interests, Personal, Other, IDMC participation: Nanobiotix; Financial Interests, Personal, Full or part-time Employment, Director of Clinical Cancer Research, Phase 1 Unit: NEXT Madrid, University Hospital Quiron Salud; Financial Interests, Personal, Stocks/Shares: 1TRIALSP; Non-Financial Interests, Member: ASCO, SEOM. L. Carter: Financial Interests, Personal, Other, Consultancy: Bicycle Therapeutics, Boehringer Ingelheim, Athenex; Financial Interests, Personal, Full or part-time Employment, Medical Advisor: Cancer research UK Centre for Drug Development; Financial Interests, Institutional, Local PI: Boehringer Ingelheim, Cellcentric, Eli Lilly, Repare Therapeutics, EMD Serono/Merck KGaA, Sierra Oncology, Nurix Therapeutics, Takeda; Financial Interests, Institutional, Coordinating PI: Bicycle Therapeutics, Athenex, Lupin Limited, Cytomx therapeutics, ADC Therapeutics; Financial Interests, Institutional, Local PI, Funding for delivering commercial trial activity: Genmab. I. Duran: Financial Interests, Personal, Advisory Board, served as advisor in the last two years: Roche Genentech, MSD, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, participated in different compensated educational activities over the last two years: Jansen, Pfizer; Financial Interests, Personal, Advisory Board, collaborated as advisor in different occasions over the last two years. Ipsen; Financial Interests, Personal, Invited Speaker, participated in different compensated educational activities over the last two years: Ipsen, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, participated in educational events sponsored by this company and received compensation for it: Merck; Financial Interests, Personal, Advisory Board, participated in different compensated advisory boards over the last two years: Astellas; Financial Interests, Personal, Advisory Board, collaborated as advisor over the last two years: Immunomedics, Inc.; Financial Interests, Personal, Invited Speaker, participated in educational activities in the last two years: EUSA Pharma, MSD; Financial Interests, Personal, Invited Speaker, participated in educational activities in the last 2 years: Novartis; Financial Interests, Personal, Invited Speaker, participated in compensated educational activities in the last two years: Astellas; Financial Interests, Personal, Invited Speaker, participated in activities as a guest speaker: Bayer; Financial Interests, Personal, Other, Bayer has covered expenses related to EAU 2023 including registration, travel and accommodation; Financial Interests, Personal, Other, AstraZeneca has covered the cost of registration, accommodation and traveling related to my attendance of ASCO GU 2024; Financial Interests, Personal, Other, Merck has covered the cost related to my attendance to ASCO 2024. (Registration, travel and accommodation); Financial Interests, Personal and Institutional, Research Grant, Roche has funded research in my institution to projects under my coordination; Financial Interests, Personal, Steering Committee Member, member of a SC for a trial sponsored by: Immunomedics, Inc.; Financial Interests, Personal and Institutional, Research Grant, AstraZeneca has funded research conducted in my institution related to a project where I am the PI; Financial Interests, Institutional, Coordinating PI, I am leading a study (Investigator initiated) that is funded by Gilead and sponsored by the foundation of my department (FUPOCAN). I am the national PI of this study and I don’t receive any compensation for this; Non-Financial Interests, Leadership Role, president of an independent cooperative group of GU Oncologist from the north of Spain: GO NORTE; Non-Financial Interests, Member of Board of Directors, member of the Board of directors since 2022: ASEICA; Non-Financial Interests, Member of Board of Directors, co-founder and member of the board of directors since 2023: GUARD (GU oncology cooperative group); Non-Financial Interests, Member of Board of Directors, Grupo Germinal is the Testicular Cancer Spanish Group, I am currently part of the board of directors since 2020 and future president of the group; Non-Financial Interests, Principal Investigator, P.I. of the PRISMA-1 study: FUPOCAN; Non-Financial Interests, Leadership Role, Co-Chair of the GU Track for ESMO Asia 2024: ESMO; Non-Financial Interests, Other, I am a member of the International Development and Education Award (IDEA) Steering Group for ASCO: ASCO; Non-Financial Interests, I am a member and co-founder of the spanish patient advocacy group in bladder cancer: CANVES. B. Garmezy: Financial Interests, Institutional, Research Funding: AbbVie, Accutar Biotechnology, Arcus Biosciences, Arvinas, AstraZeneca, AVEO Oncology, CRISPR Therapeutics, Eikon Therapeutics, Exelixis, Roche/Genentech, Flare Therapeutics, Harbour BioMed, Ideaya Biosciences, Janssen, Janux Therapeutics, Jubilant Therapeutics, Kineta, Kinnate Biopharma, Loxo, Mink Therapeutics, Nuvation Bio, Profound Bio, Takeda Therapeutics, Teon Therapeutics, Tmunity Therapeutics, Xencor, Zenshine; Financial Interests, Institutional, Speaker, Consultant, Advisor: AbbVie, Adaptimmune, AIQ Global, Amgen, Arcus Biosciences, Arvinas, AstraZeneca, AVEO Oncology, Bayer, Bicycle Tx, Eisai, EMD Serono, Exelixis, Janssen, Merck, Novartis, Pfizer, Rondo Therapeutics, Sanofi-Aventis, Seagen, Xencor. 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Falchook: Financial Interests, Institutional, Advisory Board, 2018: FujiFilm; Financial Interests, Institutional, Advisory Board, 7/24/2020, 9/17/2021: Silicon; Financial Interests, Institutional, Advisory Board, 3/10/21: Navire; Financial Interests, Institutional, Advisory Board, 4/22/21: Turning Point; Financial Interests, Institutional, Advisory Board, 10/2/21: Predicine; Financial Interests, Institutional, Advisory Board, 10/26/21: Inspirna; Financial Interests, Institutional, Advisory Board, 10/28/21: Regeneron; Financial Interests, Personal, Advisory Board, 6/2010, 3/2011: EMD Serono; Financial Interests, Institutional, Advisory Board, 1/18/22 and 8/17/22: Jubilant; Financial Interests, Institutional, Advisory Board, 6/4/22: BostonGene; Financial Interests, Institutional, Advisory Board, 9/30/22: AbbVie; Financial Interests, Personal, Invited Speaker, 2019: Total Health Conferencing; Financial Interests, Personal, Invited Speaker, 2020: Rocky Mountain Oncology Society; Financial Interests, Personal, Other, Travel, for work and/or research related to institution, 2015: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, for work and/or research related to institution, 2011, 2012, 2013: EMD Serono; Financial Interests, Personal, Other, Travel, to present research at a conference (Cholangiocarcinoma Foundation meeting), 2018: Fujifilm; Financial Interests, Personal, Other, Travel, to present research at a conference (ESGO), 2013: Millennium; Financial Interests, Personal, Other, Travel, for work and/or research related to institution, at least once yearly: Sarah Cannon Research Institute (employer); Financial Interests, Personal, Other, Travel, to present research at a conference (WCLC), 2022: Amgen; Financial Interests, Personal, Other, Travel, to present research at a conference (ESMO), 2022: Synthorx / Sanofi; Financial Interests, Institutional, Advisory Board, Scientific advisory board 11/18/22: Teon Therapeutics; Financial Interests, Institutional, Advisory Board, 12/8/22: Merck; Financial Interests, Personal, Invited Speaker, CME presentation about NSCLC and thyroid cancer, 2/20/24: Clinical Care Options; Financial Interests, Personal, Royalties: Wolters Kluwer; Financial Interests, Institutional, Local PI, Unknown end date, before 1/2021: 3-V Biosciences, ARMO/Eli Lilly, Celldex, DelMar, eFfector, Kolltan, miRNA Therapeutics, OncoMed, Precision Oncology, Strategia; Financial Interests, Institutional, Local PI, 12/2019 - 6/2023: Abbisko; Financial Interests, Institutional, Local PI, ending 4/2019: AbbVie; Financial Interests, Institutional, Local PI, 8/2021 - present: ABL Bio; Financial Interests, Institutional, Local PI, 12/2021 - 8/2023: Accutar; Financial Interests, Institutional, Local PI: Aileron, Amgen, AstraZeneca, BeiGene, Fujifilm, Jacobio, Jounce, Loxo/Bayer, Merck, Regeneron, Rgenix, Takeda; Financial Interests, Institutional, Local PI, ending 6/2014: American Society of Clinical Oncology, Celgene, EMD Serono, Genmab, MedImmune, National Institutes of Health, Oncothyreon, U.T. MD Anderson Cancer Center, Vegenics; Financial Interests, Institutional, Local PI, 9/2021 - present: Artios, NiKang; Financial Interests, Institutional, Local PI, 4/2019 - present: Bioatla; Financial Interests, Institutional, Local PI, 6/2020 - present: Bioinvent; Financial Interests, Institutional, Local PI, ending 11/2018: Biothera; Financial Interests, Institutional, Local PI, 8/2020 - present: Bicycle; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 3/2022 - present: Black Diamond, Seagen; Financial Interests, Institutional, Local PI, 5/2021 - present: Boehringer Ingelheim, Erasca; Financial Interests, Institutional, Local PI, ending 5/2021: Ciclomed; Financial Interests, Institutional, Local PI, ending 7/2018: Curegenix; Financial Interests, Institutional, Local PI, ending 3/2019: Curis; Financial Interests, Institutional, Local PI, 9/2019 - present: Cyteir, Xencor; Financial Interests, Institutional, Local PI, 11/2019 - present: Daiichi; Financial Interests, Institutional, Local PI, ending 9/2022: Eli Lilly, Tesaro; Financial Interests, Institutional, Local PI, 12/2019 - present: Epizyme; Financial Interests, Institutional, Local PI, ending 10/2023: Exelixis, GSK; Financial Interests, Institutional, Local PI, 7/2021 - present: Freenome, Samumed; Financial Interests, Institutional, Local PI, ending 10/2022: Hutchison MediPharma; Financial Interests, Institutional, Local PI, 10/2020 - present: IGM Biosciences, ImmunoGen/MarcoGenics; Financial Interests, Institutional, Local PI, ending 6/2019: Ignyta; Financial Interests, Institutional, Local PI, ending 9/2019: Incyte; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 04/2022 - present: Jubilant; Financial Interests, Institutional, Local PI, ending 5/2008, when Millennium was purchased by Takeda: Millennium; Financial Interests, Institutional, Local PI, 10/2021 - 6/2023: Molecular Templates; Financial Interests, Institutional, Local PI, 2/2021 - present: Navire; Financial Interests, Institutional, Local PI, ending 2/2024: Novartis; Financial Interests, Institutional, Local PI, 3/2020 - 2/2024: Oncorus; Financial Interests, Institutional, Local PI, 3/2020 - present: Poseida; Financial Interests, Institutional, Local PI, 12/2019 - 2/2024: Prelude; Financial Interests, Institutional, Local PI, 12/2020 - present: PureTech, Silicon; Financial Interests, Institutional, Local PI, 06/2021 - 06/2023: Pyramid; Financial Interests, Institutional, Local PI, 3/2021 - present: RasCal; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 12/2021 - present: Relay; Financial Interests, Institutional, Local PI, 8/2019 - present: Ribon, Turning Point; Financial Interests, Institutional, Local PI, 7/2020 - present: Sapience; Financial Interests, Institutional, Local PI, 12/2021 - present: Simcha; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 11/2021 - present: Sirnaomics; Financial Interests, Institutional, Local PI, ending 5/2019: Syndax; Financial Interests, Institutional, Local PI, 09/2019 - 02/2024: Synthorx/Sanofi; Financial Interests, Institutional, Local PI, ending 12/2017: Taiho; Financial Interests, Institutional, Local PI, ending 7/2022: Tarveda; Financial Interests, Institutional, Local PI, 5/2021 - present. TeneoBio was purchased by Amgen: Teneobio; Financial Interests, Institutional, Local PI, ending 1/2020: Tocagen; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 05/2022-11/2022: Metabomed; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 6/2022 - present: Agenus; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 06/2022 - present: Tallac; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 7/2022 - present: Zhuhai Yufan, Mirati; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 10/2022 - present: Immunitas, Jazz Pharmaceuticals; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 11/2022 - present: Bayer; Financial Interests, Institutional, Local PI, 1/2019 - present: ADC Therapeutics; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 3/2023 - present: Kineta, Roche; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 03/2023 - present: NGM BioPharmaceuticals; Financial Interests, Institutional, Local PI, 4/2023 - present: Tarus; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 05/2023 - present: Pyxis; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 06/2023 - present: Harbour BioMed, Centessa Pharmaceuticals; Financial Interests, Institutional, Local PI, 07/2023 - present: Ideaya, Tango Therapeutics; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 08/2023 - present: Biomea Fusion; Financial Interests, Institutional, Local PI, 09/2023 - present: Conjupro Biotherapeutics; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 09/2023 - present: Phanes Therapeutics; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 9/2023 - present: Sarah Cannon Development Innovations; Financial Interests, Institutional, Local PI, 10/20/23 - present: Nuvectis Pharma; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial, 1/20/24 - present: Kura Oncology; Financial Interests, Institutional, Local PI, 1/2024 - present: Eikon Therapeutics. L. DeMars, C. Xu, J. Bader: Financial Interests, Institutional, Full or part-time Employment: Bicycle Therapeutics; Financial Interests, Institutional, Stocks/Shares: Bicycle Therapeutics. K. Josephs: Financial Interests, Personal, Stocks/Shares: Bicycle Tx, Mersana Therapeutics. E. Fontana: Financial Interests, Personal, Invited Speaker: Caris Life Science, Repair Therapeutics; Financial Interests, Personal, Other, Conference attendance: Sapience Pharma; Financial Interests, Personal, Invited Speaker, Conference Attendance: Bicycles Therapeutics; Financial Interests, Personal, Full or part-time Employment: Hospital Corporation of America (HCA) International; Financial Interests, Personal, Officer: EORTC; Financial Interests, Institutional, Coordinating PI: Repair Therapeutics, Amgen, Taiho Pharmaceutical; Financial Interests, Institutional, Local PI: Bicycle Therapeutics, Artios Pharma, Seagen, Nurix Therapeutics, BioNTech SE, Relay Therapeutics, Pfizer, Roche, Daiichi Sankyo, Gilead Science, Basilea Pharmaceutica, Jiangsu Hengrui Medicine, Mereo Biopharma, Hutchmed, Merus, Crescendo Biologics, GSK plc, BeiGene, Turning Point Therapeutics, Sapience Pharma, Arcus Bioscience, Exelixis, Nerviano Medica, Elipsees, Deciphera, Ribon Therapeutics. All other authors have declared no conflicts of interest.