Abstract 134TiP
Background
Zelenectide pevedotin (zele, formerly BT8009) is a Bicycle® Toxin Conjugate (BTC) comprised of a highly selective bicyclic peptide targeting Nectin-4 conjugated to monomethyl auristatin E (MMAE) via a cleavable linker. Zele has shown promising antitumor activity and a generallywell tolerated safety profile in previously treated, enfortumab vedotin naïve patients with metastatic urothelial carcinoma (mUC) (Reig, 2024), and is currently being investigated as monotherapy and in combination with pembrolizumab in patients with mUC (Duravelo-2 [BT8009–230; NCT06225596]). Zele has shown preliminary clinical activity in patients with NSCLC, another tumor type associated with Nectin-4 expression.
Trial design
Duravelo-1 (BT8009-100; NCT04561362) is an ongoing, open-label dose escalation and dose expansion phase I/II study of zele monotherapy, and in combination with pembrolizumab in patients with solid tumors associated with Nectin-4 expression. Cohort B9 evaluates the safety and tolerability of zele in patients with NSCLC using a dose and schedule of zele that is under study in Duravelo-2. Adult patients with advanced or metastatic squamous or non-squamous NSCLC, negative for oncogenic driver mutations (EGFR, KRAS, ALK, BRAF, MET, ERRB2), an ECOG performance status of 0–1, and have adequate tissue for biomarker testing are eligible. Exclusion criteria for cohort B9 includes prior therapy with an antibody-drug conjugate containing an MMAE (vedotin) payload, refractory to prior taxane therapy, and grade ≥2 peripheral neuropathy. Approximately 40 patients will be treated. The primary endpoint is safety and tolerability of zelenectide pevedotin monotherapy given on a dose and schedule of 6 mg/m2 on Day 1 and 8 of a 21-day cycle. Secondary endpoints are antitumor activity including ORR, DOR, CBR, PFS and OS by Investigator assessed response, (RECIST v1.1), PK, and incidence of anti-drug antibody development. Cohort B9 opened to enrollment November 2024, and is currently recruiting patients.
Clinical trial identification
NCT04561362.
Legal entity responsible for the study
BicycleTx, Ltd.
Funding
BicycleTx, Ltd.
Disclosure
C. Baldini: Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Expert Testimony: MSD; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Invited Speaker: iTeos, AZ, Janssen, Amgen, Bicycle Therapeutics, MSD, Seattle Genetics, Tahio, Pyramid Bioscience, Tango, Roche Genentech; Non-Financial Interests, Personal, Member: ASCO, SIOG, SOFOG, AACR, ESMO. 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, Personal, 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, LV report being: 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, 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. A. Italiano: Financial Interests, Personal, Other, Contracts for services with any entity: Bayer, MSD, Merck, AstraZeneca, Roche, Novartis, Ipsen, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Bayer, MSD, Merck, AstraZeneca, Roche, Novartis, Ipsen, Daiichi, Sankyo. 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, Invited Speaker: Boehringer Ingelheim, Bicycle Therapeutics, Cellcentric, Eli Lily, Athenex, Lupin Limited, Repare Therapeutics, Cytomx therapeutics, EMD Serono/Merck KGaA, Sierra Oncology, Nurix Therapeutics, ADC Therapeutics, Takeda; Financial Interests, Institutional, Invited Speaker, Funding for delivering commercial trial activity: Genmab. G.S. 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, Invited Speaker, 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, Invited Speaker, 12/2019–6/2023: Abbisko; Financial Interests, Institutional, Invited Speaker, ending 4/2019: AbbVie; Financial Interests, Institutional, Invited Speaker, 8/2021 - present: ABL Bio; Financial Interests, Institutional, Invited Speaker, 12/2021–8/2023: Accutar; Financial Interests, Institutional, Invited Speaker: Aileron, Amgen, AstraZeneca, BeiGene, Fujifilm, Jacobio, Jounce, Loxo/Bayer, Merck, Regeneron, Rgenix, Takeda; Financial Interests, Institutional, Invited Speaker, 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, Invited Speaker, 9/2021 - present: Artios, NiKang; Financial Interests, Institutional, Invited Speaker, 4/2019 - present: Bioatla; Financial Interests, Institutional, Invited Speaker, 6/2020 - present: Bioinvent; Financial Interests, Institutional, Invited Speaker, ending 11/2018: Biothera; Financial Interests, Institutional, Invited Speaker, 8/2020 - present: Bicycle; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 3/2022 - present: Black Diamond, Seagen; Financial Interests, Institutional, Invited Speaker, 5/2021 - present: Boehringer Ingelheim, Erasca; Financial Interests, Institutional, Invited Speaker, ending 5/2021: Ciclomed; Financial Interests, Institutional, Invited Speaker, ending 7/2018: Curegenix; Financial Interests, Institutional, Invited Speaker, ending 3/2019: Curis; Financial Interests, Institutional, Invited Speaker, 9/2019 - present: Cyteir, Xencor; Financial Interests, Institutional, Invited Speaker, 11/2019 - present: Daiichi Sankyo Financial Interests, Institutional, Invited Speaker, ending 9/2022: Eli Lilly, Tesaro; Financial Interests, Institutional, Invited Speaker, 12/2019 - present: Epizyme; Financial Interests, Institutional, Invited Speaker, ending 10/2023: Exelixis, GSK; Financial Interests, Institutional, Invited Speaker, 7/2021 - present: Freenome, Samumed; Financial Interests, Institutional, Invited Speaker, ending 10/2022: Hutchison MediPharma; Financial Interests, Institutional, Invited Speaker, 10/2020 - present: IGM Biosciences, ImmunoGen/MarcoGenics; Financial Interests, Institutional, Invited Speaker, ending 6/2019: Ignyta; Financial Interests, Institutional, Invited Speaker, ending 9/2019: Incyte; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 04/2022 - present: Jubilant; Financial Interests, Institutional, Invited Speaker, ending 5/2008, when Millennium was purchased by Takeda: Millennium; Financial Interests, Institutional, Invited Speaker, 10/2021–6/2023: Molecular Templates; Financial Interests, Institutional, Invited Speaker, 2/2021 - present: Navire; Financial Interests, Institutional, Invited Speaker, ending 2/2024: Novartis; Financial Interests, Institutional, Invited Speaker, 3/2020–2/2024: Oncorus; Financial Interests, Institutional, Invited Speaker, 3/2020 - present: Poseida; Financial Interests, Institutional, Invited Speaker, 12/2019–2/2024: Prelude; Financial Interests, Institutional, Invited Speaker, 12/2020 - present: PureTech, Silicon; Financial Interests, Institutional, Invited Speaker, 06/2021–06/2023: Pyramid; Financial Interests, Institutional, Invited Speaker, 3/2021 - present: RasCal; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 12/2021 - present: Relay; Financial Interests, Institutional, Invited Speaker, 8/2019 - present: Ribon, Turning Point; Financial Interests, Institutional, Invited Speaker, 7/2020 - present: Sapience; Financial Interests, Institutional, Invited Speaker, 12/2021 - present: Simcha; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 11/2021 - present: Sirnaomics; Financial Interests, Institutional, Invited Speaker, ending 5/2019: Syndax; Financial Interests, Institutional, Invited Speaker, 09/2019–02/2024: Synthorx/Sanofi; Financial Interests, Institutional, Invited Speaker, ending 12/2017: Taiho; Financial Interests, Institutional, Invited Speaker, ending 7/2022: Tarveda; Financial Interests, Institutional, Invited Speaker, 5/2021 - present. TeneoBio was purchased by Amgen.: Teneobio; Financial Interests, Institutional, Invited Speaker, 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, Invited Speaker, 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, Invited Speaker, 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, Invited Speaker, 07/2023 - present: IDEAYA, Tango Therapeutics; Financial Interests, Institutional, Other, Subinvestigator on a sponsored clinical trial. 08/2023 - present: Biomea Fusion; Financial Interests, Institutional, Invited Speaker, 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, Invited Speaker, 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, Invited Speaker, 1/2024 - present: Eikon Therapeutics. V. Boni: Financial Interests, Personal, Advisory Board: EMD Serono, Janssen, Alentis Therapeutics; Financial Interests, Personal, Other, IDMC participation: Nanobiotix; Financial Interests, Personal, Expert Testimony: Affimed; Financial Interests, Personal, Advisory Board, Garuta Project feedback and insight: Ellipses; Financial Interests, Personal, Full or part-time Employment, DIrector of CLinical Cancer Research, Phase 1 Unit NEXT: NEXT Madrid, Universitary hospital Quiron Salud; Financial Interests, Personal, Stocks/Shares: 1TRIALSP; Financial Interests, Institutional, Invited Speaker, for trial: Affimed, Amunix; Financial Interests, Institutional, Invited Speaker: Artios, Pfizer, Hotspot Therapeutics, Constellation Pharmaceutical, AstraZeneca, Ellipses, Stemline, Debiopharm, Invox Pharma, Genmab, Genentech, Gilead, GSK, Ideaya Bioscience, Incyte, salubris biotherapeutics, Kumquat Biosciences, Lilly, Merus, Moderna, Merck Healthcare KGaA, Tubulis, Regeneron, iOMX, Revolution Medicine, Daiichi Sankyo, Scorpion Therapeutics, Totus Therapeutics, Tolrelmo Therapeutics, Tyra Bioscience, Urogen Pharma, Exelesis, Vividion Therapeutics, Zai Lab, Xencor; Financial Interests, Personal, Invited Speaker: Bycicle; Non-Financial Interests, Personal, Member: ASCO, SEOM. A. Dowlati: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Pfizer. B. Doger de Spéville: Non-Financial Interests, Personal, Principal Investigator: Bicycle therapeutics, Janssen, Immutep, AbbVie, Ascendis, AstraZeneca, BioInvent, Boehringer, Ipsen, Merk, NEC Bio Therapeutics, Novartis, Revolution, Roche, Takeda, Zai Lab, Totus Medicines, BioNTech, Enliven. E. Fontana: Financial Interests, Personal, Invited Speaker: CARIS Life Science, Repair Therapeutics; Financial Interests, Personal, Other, Conference attendance: Sapience Pharma, SEAGEN, ERASCA; Financial Interests, Personal, Invited Speaker, Conference Attendance: Bicycles Therapeutics; Financial Interests, Personal, Advisory Board: Astellas, Pfizer, Bicycles Therapeutics, BMS; Financial Interests, Personal, Full or part-time Employment: Hospital Corporation of America (HCA) International; Financial Interests, Personal, Officer: EORTC; Financial Interests, Institutional, Invited Speaker: Repair Therapeutics, Bicycle Therapeutics, Artios Pharma, Seagen, Amgen, Nurix Therapeutics, BioNTech SE, Relay Therapeutics, Taiho Pharmaceutical, 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, Erasca, PMV Pharma, Takeda, Acerta Pharma, ADC Therapeutics, Array Biopharma, Astellas, Astex, AstraZeneca, Bayer, BluePrint, Boehringer Ingelheim, Calithera, Carrick Therapeutics, Casi Therapeutics, Clovis Oncology, CytomX Therapeutics, EliLilly, Fore Biotherapeutics, G1 Therapeutics, Genentech, H3 Biomedicine, Immunocore, Immunomedics, Incyte, Instil Bio, Iovance, Janssen, Kronos Bio, Lupin Limited, Macrogenics, Menarini, Merck KGaA, MIllenium Pharmaceuticals, MSD, Oncologie, Oxford Vacmedix, Plexxikon, QED Therapeutics, Servier, Synthon Biopharmaceuticals, Tesaro. J. Rodon: Financial Interests, Personal, Advisory Board: Ellipses Pharma, IONCTURA SA, Aadi Bioscience, Envision Pharma, Molecular Partners, Mekanistic, Amgen; Financial Interests, Personal, Other, Consultancy: Clarion Healthcare, Debiopharm, Cullgen, Pfizer, Macrogenics, Oncology One, Columbus Venture Partners, Sardona Therapeutics, Avoro Capital Advisors, Vall d’Hebron Institute of Oncology/Ministero De Empleo Y Seguridad, Chinese University of Hong Kong, Boxer Capital, LLC, Tang Advisors, LLC, Alnylam Pharmaceuticals, Bridgebio Pharma; Financial Interests, Personal, Other, Consultancy/Advisory Board: Monte Rosa Therapeutics, Merus N.V., Incyte; Financial Interests, Institutional, Other, Clinical Research: Novartis, Spectrum Pharmaceuticals, Symphogen, BioAtla, Pfizer, GenMab, CytomX, Kelun-Biotech, Takeda-Millenium, GSK; Financial Interests, Institutional, Other, Research Funding: Blueprint Medicines, Black Diamond, Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant, Research Funding/Clinical Research: Hummingbird, Yingli; Financial Interests, Institutional, Research Grant, Research Funding: Vall d’Hebron Institute of Oncology/Cancer Core Europe; Financial Interests, Institutional, Research Grant, Clinical Research: Bicycle Therapeutics, Taiho, Roche Pharmaceuticals, Merus, Curis, AadiBioscience, Nuvation, ForeBio, BioMed Valley Discoveries, Loxo Oncology, Cellestia, Deciphera, Ideaya, Amgen, Tango Therapeutics, Mirati, Linnaeus Therapeutics, Bayer, Hutchinson MediPharma; Other, Personal, Other: VHIO/Ministero De Empleo Y Seguridad Social; Other, Personal, Other, Travel: European Society for Medical Oncology, Loxo Oncology. C. Vicier: Financial Interests, Personal, Speaker’s Bureau: Seagen, AstraZeneca, Pfizer; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Novartis, Pfizer; Financial Interests, Personal, Advisory Board: Pfizer, Daiichi Sankyo Novartis. R. Balaraman: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Genentech; Financial Interests, Personal, Advisory Role: AstraZeneca/MedImmune, Genentech; Financial Interests, Personal, Funding, Research Funding: Tizona Therapeutics, Inc. (Inst). L. Demars: Financial Interests, Personal, Full or part-time Employment: Bicycle Therapeutics; Financial Interests, Personal, Stocks/Shares: Bicycle Therapeutics; Financial Interests, Personal, Full or part-time Employment, Jan 2022-Sept 2023: Mersana Therapeutics. G. Brown: Financial Interests, Personal, Full or part-time Employment: Bicycle Therapeuitcs; Financial Interests, Personal, Stocks/Shares: Bicycle Therapeuitcs. C. Xu: Financial Interests, Personal, Full or part-time Employment: Bicycle Therapeuitcs; Financial Interests, Personal, Stocks/Shares: Bicycle Therapeuitcs. J. Bader: Financial Interests, Personal, Full or part-time Employment: Bicycle Therapeuitcs; Financial Interests, Personal, Stocks/Shares: Bicycle Therapeuitcs. M. McKean: Financial Interests, Institutional, Other, Consulting: Pfizer, Castle Biosciences, IQVIA, Merck, Moderna; Financial Interests, Institutional, Research Grant: Acentage Pharma Group, Bicycle Therapeutics, Dragonfly Therapeutics, Epizyme, Exelixis, Genentech, GSK, IDEAYA Biosciences, Ikena Oncology, Infinity Pharmaceuticals, Jacobio Pharmaceuticals, Moderna, NBE Therapeutics, Novartis, Oncorus, Plexxicon, Prelude Therapeutics, Regeneron, Sapience Therapeutics, Seattle Genetics, Tizona Therpeutics, TMUNITY Therapeutics, TopAlliance Biosciences, Aadi Biosciences, Alpine Immune Sciences, Arcs Biosciences, Arvinas, ASCO, Astellas, Bayer, BioMed Valley Discoveries, BioNTech, C4 Therapeutics, EMD Serono, Erasca, Foghorn Therapeutics, G1 Therapeutics, Gilead Sciences, ImmVira Pharma, Kechow Pharma, Kezar Life Sciences, Kinnate BioPharma, MedImmune, Mereo BioPharma, Metabomed, Nektar, OncoC4, PACT Pharma, Pfizer, Poseida, Pyramid Biosciences, Scholar Rock, Synthrox, Takeda Pharmaceuticals, Teneobio, Tempest Therapeutics, Xilio, Aulos Bioscienc, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, InconVir, Jazz Pharmaceutical, Krystal Biotech, NucMito Pharmaceuticals, OnKure, Remix Therapeutics. All other authors have declared no conflicts of interest.