First-in-Human Study of ATX-295, an Oral Inhibitor of KIF18A, as Monotherapy and in Combination With Anticancer Therapy in Patients With Advanced or Metastatic Solid Tumors, Including Ovarian Cancer

ATX-295 is an oral drug that inhibits a protein called KIF18A, an adenosine triphosphate (ATP)-dependent, plus end-directed mitotic kinesin. KIF18A facilitates chromosomal alignment and spindle microtubule dynamics during mitosis in certain advanced solid tumors. ATX-295 has been shown preclinically to induce robust anti-tumor activity of a variety of different solid tumors, including high-grade serious ovarian cancer, squamous non-small cell lung cancer, and triple negative breast cancer. This is a first-in-human, Phase 1, open-label, single-arm, dose-escalation and Simon 2-Stage expansion study to evaluate the safety profile of ATX-295 and determine the recommended phase 2 dose (RP2D) as a monotherapy and in combination with bevacizumab (or a biosimilar). In addition, the study aims to characterize the PK, PD, and preliminary anti-tumor activity of orally administered ATX-295 as a monotherapy and in combination with bevacizumab (or a biosimilar). Exploratory objectives include examination of biomarker responses in relationship to ATX-295 exposure. Patients with locally advanced or metastatic high-grade serious ovarian cancer and squamous non-small cell lung cancer will be enrolled to preliminarily assess the anti-tumor effect, and further examine the safety and PK of ATX-295 at the RP2D.