Abstract 1496TiP
Background
Advanced G/GEJ adenocarcinoma is associated with a poor prognosis, therefore new treatments are urgently needed. CLDN18.2, a tight junction protein, is an epithelial surface marker for various malignancies, including G/GEJ adenocarcinoma. Its expression on normal cells is limited to differentiated epithelial cells of the gastric mucosa and small intestine. AMG 910 is a half-life extended (HLE) BiTE® (bispecific T cell engager) antibody construct designed to engage CD3-positive T cells with CLDN18.2-expressing G/GEJ adenocarcinoma cells and thus mediate redirected tumor cell lysis. This first-in-human, phase I, open-label study (NCT04260191) is evaluating AMG 910 in patients with CLDN18.2-positive G/GEJ adenocarcinoma.
Trial design
Key eligibility criteria include patients aged ≥18 years with histologically or cytologically confirmed metastatic or locally advanced unresectable CLDN18.2-positive G/GEJ adenocarcinoma, ineligible for curative surgery who are refractory to or have relapsed following ≥2 prior lines that included a platinum, a fluoropyrimidine, a taxane or irinotecan, and an approved vascular endothelial growth factor receptor antibody or tyrosine kinase inhibitor. Patients eligible for human epidermal growth factor receptor-2 (HER2) directed therapy should have received an approved HER2-targeting antibody. Primary endpoints include dose-limiting toxicities, treatment-emergent and treatment-related adverse events, and changes in vital signs, electrocardiogram, and laboratory tests. Secondary endpoints include pharmacokinetics of AMG 910, objective response, duration of response, time to progression, 6-month and 1-year progression-free survival, and 1- and 2-year overall survival. The dose-exploration phase (n≤34) will estimate the maximum tolerated dose (MTD) and a recommended phase II dose based on safety, efficacy, and pharmacodynamic data prior to reaching an MTD. This will be followed by a dose-expansion phase (n≤36) to confirm the benefit/risk profile of AMG 910. The study is open for recruitment of patients in North America, Europe, and Asia.
Clinical trial identification
NCT04260191 - Feb 7, 2020.
Editorial acknowledgement
Swapnil Kher, PhD of Cactus Lifesciences (part of Cactus Communications) provided medical writing support and was funded by Amgen Inc.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
F. Lordick: Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self): Astra Zeneca; Honoraria (self), Advisory/Consultancy: Astellas; Honoraria (self): BioNTech; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self): Elsevier; Honoraria (self): Excerpta Medica; Honoraria (self): Imedex; Honoraria (self): Infomedica; Honoraria (self), Research grant/Funding (self): Lomedico AG; Honoraria (self): Medscape; Honoraria (self): MedUpdate GmbH; Honoraria (self), Advisory/Consultancy: Merck Sharp & Dohme; Honoraria (self), Advisory/Consultancy: Merck Serono; Honoraria (self): Onkovis GmbH; Honoraria (self): Promedicis; Honoraria (self): Springer Nature Group; Honoraria (self): StreamedUp!; Honoraria (self), Advisory/Consultancy: Zymeworks; Travel/Accommodation/Expenses: Roche. J. Chao: Honoraria (self), Research grant/Funding (self): Merck Sharp & Dohme; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: MacroGenics; Advisory/Consultancy, Travel/Accommodation/Expenses: Foundation Medicine; Research grant/Funding (self): Brooklyn Immunotherapeutics. H.W.M. van Laarhoven: Advisory/Consultancy, Research grant/Funding (self): BMS; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (self): Nordic Pharma; Advisory/Consultancy, Research grant/Funding (self): Servier; Research grant/Funding (self): Philips; Research grant/Funding (self): Roche. C.M.R. Lima: Honoraria (self), Speaker Bureau/Expert testimony: Celgene; Speaker Bureau/Expert testimony: Merck; Honoraria (self), Speaker Bureau/Expert testimony: Eisai; Honoraria (self), Speaker Bureau/Expert testimony: Taiho Pharmaceutical; Honoraria (self): Xcenda; Research grant/Funding (self): Rafael Pharmaceuticals; Research grant/Funding (self): Boston Biomedical; Research grant/Funding (self): Pharmacyclics. F. Dayyani: Spouse/Financial dependant: Roche Diagnostics USA; Advisory/Consultancy, Speaker Bureau/Expert testimony: Genentech; Advisory/Consultancy, Speaker Bureau/Expert testimony: Exelixis; Advisory/Consultancy: FMI; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy: QED; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Genentech; Speaker Bureau/Expert testimony: Sirtex; Research grant/Funding (self): BMS; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): Merck; Speaker Bureau/Expert testimony, Research grant/Funding (self): Amgen; Research grant/Funding (self): Aveo; Licensing/Royalties: Roche Diagnostics. V. Heinemann: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Sirtex; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Servier; Honoraria (self): Pfizer; Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy, Research grant/Funding (self): Boehringer Ingelheim; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Celgene; Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer. R. Greil: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Celgene; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Takeda; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Novartis; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: BMS; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: MSD; Honoraria (self), Research grant/Funding (self): Sandoz; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AbbVie; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Gilead; Honoraria (self), Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen. S. Stienen: Shareholder/Stockholder/Stock options, Licensing/Royalties: Amgen. K. Shitara: Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self): Yakult; Advisory/Consultancy, Research grant/Funding (self): Astellas Pharma; Advisory/Consultancy, Research grant/Funding (self): Eli Lilly; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pfizer; Advisory/Consultancy, Research grant/Funding (self): Ono Pharmaceutical; Advisory/Consultancy, Research grant/Funding (self): Taiho; Advisory/Consultancy, Research grant/Funding (self): MSD; Honoraria (self), Advisory/Consultancy: Novartis; Advisory/Consultancy: GlaxoSmithKline; Research grant/Funding (self): Sumitomo Dainippon Pharma; Research grant/Funding (self): Daiichi Sankyo; Research grant/Funding (self): Chugai Pharm; Research grant/Funding (self): Astellas Pharma; Research grant/Funding (self): Medi Science. All other authors have declared no conflicts of interest.