A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies
Advanced solid tumor that is refractory or intolerant to standard of care therapy, where the tumor is pancreatic adenocarcinoma (no molecular typing) or any other solid tumor that has a documented activating mutation, amplification, or fusion of HER2, ERBB3, FGFR1, FGFR2, or an activating mutation in KRAS.
Zotatifin is a novel small-molecule, investigational drug being developed by eFFECTOR Therapeutics as an anticancer therapy. Zotatifin is a potent and selective inhibitor of eIF4A1-mediated translation and selectively regulates the translation of a subset of mRNAs based on sequence specific recognition motifs in their 5′-UTR. eIF4A1 inhibition by zotatifin downregulates expression of receptor tyrosine kinases and KRAS, leading to decreased signaling through the PI3K/AKT and MAPK pathways. Preclinical efficacy testing of zotatifin demonstrates activity across models of solid tumor cancers with amplifications in HER2, FGFR1/2 and mutations in KRAS (including breast, NSCLC and CRC).
The Phase 1 dose escalation portion of this trial has been completed and zotatifin is currently being evaluated in Phase 2a expansion cohorts in certain biomarker-positive solid tumors, including ER+ breast cancer and KRAS-mutant NSCLC.