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.
Joseph Chao, Elvira Buxó, Andrés Cervantes, Farshid Dayyani, Caio Max Sao Pedro Rocha Lima, Richard Greil, Hanneke W.M. van Laarhoven, Sylvie Lorenzen, Volker Heinemann, Roman Kischel, Kohei Shitara, Florian Lordick
Abstract
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: [email protected] . Clinical trial information: NCT04117958 .