Clinical trial NCT06799065: First-in-Human Study of ATX-295, an Oral Inhibitor of KIF18A, in Patients With Advanced or Metastatic Solid Tumors, Including Ovarian Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Breast Cancer Recurrent
Ovarian Cancer
High-grade Serous Ovarian Carcinoma
Triple Negative Breast Cancer
Keywords: KIF
KIF18A
HGSOC
Platinum-resistant
Platinum-intolerant
Platinum-refractory
Lead sponsor: Accent Therapeutics
Sponsor class: INDUSTRY
First posted: 2025-01-29
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of ATX-295
timeFrame: 12 months
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
timeFrame: 12 months
Secondary outcomes:
measure: Preliminary evidence of antitumor activity
timeFrame: 12 months
measure: Measurement of phospho-histone H3 in pre- and post-treatment biopsies for a subset of participants (pharmacodynamic biomarker)
timeFrame: 12 months
measure: Maximum observed plasma concentration of ATX-295 (Cmax)
timeFrame: 12 months
measure: Calculated time to reach maximum observed plasma concentration (Tmax)
timeFrame: 12 months
measure: Calculated area under the plasma concentration-time curve of ATX-295 (AUC0-t)
timeFrame: 12 months
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
References: