First-in-Human Study of ATX-295, an Oral Inhibitor of KIF18A, in Patients With Advanced or Metastatic Solid Tumors, Including Ovarian Cancer
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: ATX-295.
- Who it may be relevant to
- Registry conditions: Advanced Solid Tumors, Breast Cancer Recurrent, Ovarian Cancer, High-grade Serous Ovarian Carcinoma. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
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
Overview
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.
Interventions
- Drug ATX-295
ATX-295 Tablets will be taken orally
Primary outcome measures
- Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of ATX-295 [Time frame: 12 months]
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [Time frame: 12 months]
Secondary outcome measures (5)
- 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
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
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Sequential
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 6 centers
- Florida Cancer Specialists — Sarasota
- Karmanos Cancer Institute — Detroit
- SCRI Oncology Partners — Nashville
- MD Anderson Cancer Center — Houston
- NEXT Oncology — San Antonio
- NEXT Virginia — Fairfax
Identifiers
NCT: NCT06799065 · ATX-295-001