First-in-Human Study of ATX-295, an Oral Inhibitor of KIF18A, in Patients With Advanced or Metastatic Solid Tumors, Including Ovarian Cancer

Phase 1

Recruiting

• Conditions: Advanced Solid Tumors; Breast Cancer Recurrent; Ovarian Cancer; High-grade Serous Ovarian Carcinoma; Triple Negative Breast Cancer
• Interventions: Drug: ATX-295

• Registration Number: NCT06799065
• Lead Sponsor: Accent Therapeutics

Brief 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.

Study Timeline

• Study First Submitted: 2025-01-18
• Study First Submitted QC: 2025-01-23
• Study First Posted: 2025-01-29
• Study Start: 2025-03-21
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-12
• Last Update Posted: 2025-06-13
• Primary Completion: 2027-04-30
• Study Completion: 2027-08-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 65

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Expansion: Platinum-Resistant, -Refractory, or -Intolerant HGSOC	ATX-295	-
Dose Escalation	ATX-295	Subjects will be enrolled at various doses and/or schedules of ATX-295 to identify the expansion dose(s) and RP2D

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)	12 months	Adverse events graded according to CTCAE v5.0
Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of ATX-295	12 months	Identification of a tolerable and safe dose for expansion cohorts based on dose limiting toxicities

Secondary Outcome Measures

Name	Time	Method
Preliminary evidence of antitumor activity	12 months	Objective response rate based on RECIST v1.1
Measurement of phospho-histone H3 in pre- and post-treatment biopsies for a subset of participants (pharmacodynamic biomarker)	12 months
Maximum observed plasma concentration of ATX-295 (Cmax)	12 months
Calculated time to reach maximum observed plasma concentration (Tmax)	12 months
Calculated area under the plasma concentration-time curve of ATX-295 (AUC0-t)	12 months

Trial Locations

Locations (4)

Florida Cancer Specialists; 🇺🇸 Sarasota, Florida, United States

SCRI Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

NEXT Oncology; 🇺🇸 San Antonio, Texas, United States