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RecruitingInterventionalPhase 1

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

NCT ID: NCT06799065Sponsor: Accent TherapeuticsLast updated: 2026-02-24

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

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Key Inclusion Criteria: * Patients with histologically confirmed solid tumors who have locally recurrent or metastatic disease, including HGSOC * Refractory to or relapsed after all standard therapies with proven clinical benefit, unless as deemed by the Investigator, the subject is not a candidate for standard treatment, there is no standard treatment, or the subject refuses standard treatment after expressing an understanding of all available therapies with proven clinical benefit * For the expansion cohorts, participants must have histological confirmation of HGSOC and be determined to be platinum-resistant, platinum-refractory, or platinum-intolerant * There is no limit to the number of prior treatment regimens * Have measurable or evaluable disease * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Key Exclusion Criteria: * Clinically unstable central nervous system (CNS) tumors or brain metastasis * Any other concurrent anti-cancer treatment, except for hormonal blockade * Has undergone a major surgery within 3 weeks of starting study treatment * Medical issue that limits oral ingestion or impairment of gastrointestinal function that is expected to significantly reduce the absorption of ATX-295, however participants with a functioning distal ileostomy or colostomy may be permitted on trial * Clinically significant (ie, active) or uncontrolled cardiovascular disease * Need to use proton pump inhibitors on study or H2-receptor antagonists for the dose escalation portion of the study. * Unable to transition off strong or moderate CYP3A4 inhibitors or strong inducers * Pregnancy or intent to breastfeed or conceive a child within the projected duration of treatment Other inclusion and exclusion criteria as defined in the study protocol

Study locations (5)

Florida Cancer Specialists

Sarasota, Florida, 34232

Recruiting
Latisha Hall · Contact
Judy Wang, MD · Principal Investigator

SCRI Oncology Partners

Nashville, Tennessee, 37203

Recruiting
Latisha Hall · Contact
Deepak Bhamidipati, MD · Principal Investigator

MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Timothy Yap, MD, PhD · Contact
Timothy Yap, MD, PhD · Principal Investigator

NEXT Oncology

San Antonio, Texas, 78229

Recruiting
Ildefonso Ismael Rodriguez Rivera, MD · Principal Investigator

NEXT Virginia

Fairfax, Virginia, 22031

Recruiting
Maybelle De La Rosa · Contact
Alexander Spira, MD, PhD, FACP · Principal Investigator