A Phase 1/2, Open-Label, Dose-Escalation and Expansion First-In-Human Study of ATX-295, an Oral Inhibitor of the Kinesin Motor Protein KIF18A, in Patients With Locally Advanced or Metastatic Solid Tumors, Including High-Grade Serous Ovarian Cancer
Summary
The goal of this study is to identify a safe and tolerated dose of the orally administered KIF18A inhibitor ATX-295. In addition, this study will evaluate the pharmacokinetics, pharmacodynamics and preliminary antitumor activity of ATX-295 in patients with advanced solid tumors and ovarian cancer.
Detailed description
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 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). In addition, the study aims to characterize the PK, PD, and preliminary anti-tumor activity of orally administered ATX-295. Exploratory objectives include examination of biomarker responses in relationship to ATX-295 exposure. Patients with locally advanced or metastatic solid tumors will be enrolled to preliminarily assess the anti-tumor effect, and further examine the safety and PK of ATX-295 at the RP2D.
Arms & interventions
- DrugATX-295
ATX-295 Tablets will be taken orally
Outcome measures
Primary
Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of ATX-295
Identification of a tolerable and safe dose for expansion cohorts based on dose limiting toxicities
Time frame: 12 months
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Adverse events graded according to CTCAE v5.0
Time frame: 12 months
Secondary
Preliminary evidence of antitumor activity
Time frame: 12 months
Measurement of phospho-histone H3 in pre- and post-treatment biopsies for a subset of participants (pharmacodynamic biomarker)
Time frame: 12 months
Maximum observed plasma concentration of ATX-295 (Cmax)
Time frame: 12 months
Calculated time to reach maximum observed plasma concentration (Tmax)
Time frame: 12 months
Calculated area under the plasma concentration-time curve of ATX-295 (AUC0-t)
Time frame: 12 months
Eligibility criteria
Study locations (5)
Florida Cancer Specialists
Sarasota, Florida, 34232
SCRI Oncology Partners
Nashville, Tennessee, 37203
MD Anderson Cancer Center
Houston, Texas, 77030
NEXT Oncology
San Antonio, Texas, 78229
NEXT Virginia
Fairfax, Virginia, 22031