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RESEARCH PRODUCT

Trial in progress: A phase I study of AMG 199, a half-life extended bispecific T-cell engager (HLE BiTE) immune therapy, targeting MUC17 in patients with gastric and gastroesophageal junction (G/GEJ) cancer.

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TPS4649 Background: Prognosis for advanced G/GEJ cancer is poor and new treatment modalities are urgently needed. MUC17 is a transmembrane protein overexpressed and differentially localized on the cell membrane of G/GEJ cancer cells; expression and localization in normal cells is much more limited. AMG 199 is an HLE BiTE immune therapy designed to engage CD3-positive T cells to MUC17-positive G/GEJ cancer cells, mediate redirected tumor cell lysis, and induce T cell activation and proliferation. A clinical trial is being conducted for this novel and targeted immune therapy agent in patients with MUC17-positive G/GEJ cancer. Methods: This is a first-in-human phase 1, open-label, dose escalating study (NCT04117958) evaluating AMG 199 in patients with MUC17-positive G/GEJ cancer. Key eligibility criteria include metastatic or locally advanced unresectable MUC17-positive (as determined by IHC using a central laboratory assay) gastric adenocarcinoma or gastroesophageal junction adenocarcinoma ineligible for curative surgery and relapsed or treatment-refractory following ≥2 lines including a platinum, a fluoropyrimidine, 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 or -related adverse events, vital signs, electrocardiogram (ECG), and laboratory changes. Secondary endpoints include: pharmacokinetics of AMG 199, objective response, duration of response, time to progression, 6-month and 1-year progression-free survival, and 1-year and 2-year overall survival. The dose exploration (n = 30) will estimate the maximum tolerated dose and/or recommended phase 2 dose; this will be followed by a dose expansion (n = 40) and evaluation of the benefit/risk profile of AMG 199. The study began enrolling patients in January 2020 and is ongoing. This is the first clinical trial to investigate MUC17 as a potential anti-tumor target. For more information, please contact Amgen Medical Information: medinfo@amgen.com . Clinical trial information: NCT04117958 .