Abstract 1779TiP
Background
More than 212,000 deaths annually are related to bladder cancer worldwide (Sung 2021), with 5-year survival rates of <5% in metastatic urothelial carcinoma (UC) (Witjes 2021). Nearly half of all pts cannot tolerate standard cisplatin-based first line (1L) chemotherapy and opportunity still exists to improve outcomes in both 1L and later lines of therapy. Human epidermal growth factor receptor 2 (HER2) is overexpressed in multiple malignant tumors and overexpression of HER2 may be associated with poor outcomes in UC (Zhao 2015). No HER2-directed therapies are currently approved for locally advanced unresectable or metastatic UC (LA/mUC). Disitamab vedotin (DV; RC48-ADC) is an investigational antibody–drug conjugate (ADC) comprised of a HER2-directed monoclonal antibody conjugated to monomethyl auristatin E (MMAE) via a protease-cleavable linker. DV elicits antitumor activity through MMAE-directed cytotoxicity and bystander effect (Li 2020). DV is conditionally approved in LA/mUC and gastric cancer in China and was granted Breakthrough Therapy designation by the FDA for second-line treatment of HER2-expressing LA/mUC after platinum-containing chemotherapy.
Trial design
RC48G001 (NCT04879329) is a phase 2, multicohort, open-label, multicenter trial to evaluate DV in pts with HER2-expressing LA/mUC. Pts are enrolled in 2 cohorts defined by HER2 expression (by immunohistochemistry [IHC]) and gene amplification (by in situ hybridization [ISH]) by central laboratory: Cohort A (IHC 3+, or 2+ and ISH+) and Cohort B (IHC 2+ and ISH-, or IHC 1+). Eligible pts must have measurable disease per RECIST v1.1, ECOG Performance Status of 0 or 1, and must have received 1 or 2 lines of prior systemic therapy, including 1 line of platinum-containing chemotherapy. The primary endpoint is confirmed objective response rate (ORR) assessed by blinded independent central review. Secondary endpoints include ORR assessed by investigator, duration of response, progression-free survival, disease control rate, overall survival, safety, and pharmacokinetic parameters. Enrollment for cohorts A and B is ongoing in North America and EU, and planned in LATAM, APAC, and Israel.
Clinical trial identification
NCT04879329.
Editorial acknowledgement
Under guidance of the authors, assistance in medical writing was provided by Hanna Thomsen, PhD, of Seagen Inc. and was funded by Seagen Inc. in accordance with Good Publication Practice (GPP3) guidelines.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
V.S. Koshkin: Financial Interests, Personal, Other, Consulting or Advisory Role: Janssen, AstraZeneca, Dendreon, Gerson Lehrman Group, Guidepoint Global, Clovis Oncology, Pfizer/EMD Serono, Seagen Inc.; Financial Interests, Personal, Research Grant, Research Funding: Clovis Oncology, Nektar, Endocyte, Janssen Oncology; Financial Interests, Institutional, Research Grant, Research Funding: Taiho Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Janssen. T.B. Powles: Financial Interests, Personal, Other, Consultancy: Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Incyte, Ipsen, Johnson&Johnson, Merck Serono, Merck, MSD, Novartis, Pfizer, Roche, Seagen Inc., Mashup Ltd.; Financial Interests, Personal, Research Grant, Research Funding/Grants: Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Exelixis, Ipsen, Johnson&Johnson, Merck Serono, Merck, MSD, Novartis, Pfizer, Roche, Seagen Inc.; Financial Interests, Personal, Other, Travel Expenses: AstraZeneca, Ipsen, MSD, Pfizer, Roche. G. Iyer: Financial Interests, Personal, Other, Consultancy: Bayer, Janssen, Mirati Therapeutics, Basilea, Flare Therapeutics, LOXO/Lilly; Financial Interests, Personal, Speaker’s Bureau, Speaker’s Bureau: Gilead Sciences, The Lynx Group; Financial Interests, Personal, Research Grant, Research Funding/Grants: Mirati Therapeutics, Novartis, Debiopharm, Bayer, Janssen, Seagen Inc. Y. Loriot: Financial Interests, Institutional, Research Grant, Grants or contracts from any entity: Janssen, Celsius, MSD; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS, Pfizer, Merck Kg, MSD, AstraZeneca, Roche, Janssen, Astellas, Seagen Inc., Immunomedics; Financial Interests, Institutional, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: BMS, Pfizer, Janssen, Merck Kg; Financial Interests, Personal, Other, Support for attending meetings and/or travel: BMS, Roche, AstraZeneca, MSD, Pfizer. A. Drakaki: Financial Interests, Personal, Advisory Board, Advisory Board Membership: SG, Merck, Roche, Exelixis. I. Duran Martinez: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Ipsen, Roche-Genentech, Astellas Pharma, EUSA Pharma, Bayer, Novartis, Eisai, Debio Pharma, Pharmacyclycs; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, MSD, Ipsen, Roche-Genentech, Janssen, Astellas Pharma, EUSA Pharma, Bayer, Novartis, Gilead; Financial Interests, Personal, Research Grant, Research Funding/Grants: Roche, AstraZeneca; Financial Interests, Personal, Other, Travel Expenses: Pzifer-Merck, Ipsen. M. De Santis: Financial Interests, Personal, Advisory Board: AAA, Amgen, Astellas, AstraZeneca, Basilea, Bayer, Bioclin, BMS, Eisai, Ferring, Immunomedics, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, Seagen Inc.; Financial Interests, Personal, Other, Consultancy: AAA, Merck, MSD; Financial Interests, Personal, Other, Honoraria: AAA, Amgen, Astellas, AstraZeneca, Basilea, Bayer, Bioclin, BMS, EISAI, Ferring, Immunomedics, Ipsen, Janssen, MSD, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, Seagen Inc.; Financial Interests, Personal, Other, Travel Expenses: EAU, Janssen, Bayer, MSD, Merck, Sanofi. M. Retz: Financial Interests, Personal, Advisory Board: BMS, Janssen-Cilag, MSD; Financial Interests, Personal, Full or part-time Employment, Employment: Rechts der Isar Medical Center, Technical University Munich, Germany. R.K. Jain: Financial Interests, Personal, Advisory Board: Gilead, BMS, Aveo Pharma, Seagen Inc.; Financial Interests, Personal, Speaker’s Bureau: Seagen Inc., Gilead; Financial Interests, Personal, Funding, Research Funding: BMS, CTEP; Financial Interests, Personal, Other, Honoraria: NCCN. S. Chan: Financial Interests, Personal, Full or part-time Employment, employee and stockholder: Seagen Inc. M. Ichimaru: Financial Interests, Personal, Full or part-time Employment, employee and stockholder: Seagen. M.D. Galsky: Financial Interests, Personal, Other, Consultancy: Aileron, Astellas, AstraZeneca, Basilea, BioMotiv, Bristol Myers Squibb, Dendreon, Dracen, Dragonfly, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Incyte, Infinity, Inovio, Janssen, Lilly, Merck, Novartis, NuMab, Pfizer, Seagen Inc., UroGen; Financial Interests, Personal, Ownership Interest, Equity Ownership: Rappta; Financial Interests, Personal, Royalties, Patents and Royalties: Methods and Compositions for treating cancer and related methods. mount sinal school of medicine July 2012 Application number: 20120322792; Financial Interests, Personal, Research Grant, Research Funding/Grants: AstraZeneca, Bristol Myers Squibb, Dendreon, Gententech/Roche, Janssen, Merck, Novartis.