First-In-Human Phase 1 Study of ETC-159, an Oral PORCN Inhibitor in Patients with Advanced Solid Tumors

The phase 1 study of ETC-159, an oral PORCN inhibitor, involved 16 patients with advanced solid tumors to assess its safety, dosage, and effects on Wnt signaling. The study found that ETC-159 was well tolerated at doses that inhibited Wnt signaling, with the most common adverse events being vomiting, anorexia, and fatigue. Pharmacodynamic effects, such as reduced AXIN2 mRNA levels in blood and hair follicles, were observed from a 4 mg dose. Although no tumor responses were seen, two patients experienced stable disease. The study highlighted the need for early monitoring of bone turnover due to increased β-CTX levels and reduced bone density in some patients.