KTM-101

KTM-101 is a brain-penetrant, reversible, and highly selective small molecule inhibitor of the epidermal growth factor receptor (EGFR). Developed by Katmai Oncology, it is specifically engineered to cross the blood-brain barrier, exhibiting an exceptionally high brain-to-plasma ratio (ranging from 3.9 to 13 across species) to address the challenges of treating central nervous system tumors. KTM-101 demonstrates broad activity against both amplified wild-type EGFR and extracellular domain mutants, such as EGFRvIII, which are common in glioblastoma (GBM). Preclinical studies in patient-derived orthotopic xenograft models have shown significant efficacy, including an objective response rate of 43%. It is currently undergoing Phase 1 clinical evaluation (NCT05222802) for patients with recurrent EGFR-altered glioblastoma, with preliminary evidence supporting clinical activity.