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)
Clinical Trial Description:
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.