First-in-Human Study of ATX-295, an Oral Inhibitor of KIF18A, as Monotherapy and in Combination With Anticancer Therapy in Patients With Advanced or Metastatic Solid Tumors, Including Ovarian Cancer
Sponsor: Accent Therapeutics
ClinicalTrials ID:NCT06799065
This Phase 1 study evaluates the safety, pharmacokinetics, and preliminary antitumor activity of ATX-295, an oral KIF18A inhibitor, alone and with bevacizumab. Eligible patients have advanced solid tumors, including ovarian and lung cancer, and must have relapsed or be refractory to standard treatments. ATX-295 is administered orally, with bevacizumab given intravenously in combination therapy.
Patient Parameters
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Program 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 as a monotherapy and in combination with bevacizumab (or a biosimilar) in patients with locally advanced or metastatic solid tumors, including ovarian cancer and lung cancer.
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, squamous non-small cell lung 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) as a monotherapy and in combination with bevacizumab (or a biosimilar). In addition, the study aims to characterize the PK, PD, and preliminary anti-tumor activity of orally administered ATX-295 as a monotherapy and in combination with bevacizumab (or a biosimilar). Exploratory objectives include examination of biomarker responses in relationship to ATX-295 exposure.
Patients with locally advanced or metastatic high-grade serious ovarian cancer and squamous non-small cell lung cancer 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
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 monotherapy expansion cohorts:
- Participants must have histological confirmation of HGSOC and be determined to be platinum-resistant, or platinum-intolerant
- Participants with sqNSCLC should have received prior treatment with a platinum, taxane, and checkpoint inhibitor
- For the combination with bevacizumab (or biosimilar): Participants must have histologically confirmed HGSOC or select solid tumors
- There is no limit to the number of prior treatment regimens
- Have measurable disease; evaluable disease is acceptable during dose escalation
- 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
Locations
| FACILITY | ZIP | CITY | STATE |
|---|---|---|---|
| University of Colorado Denver | 80045 | Aurora | Colorado |
| Florida Cancer Specialists | 34232 | Sarasota | Florida |
| Karmanos Cancer Institute | 48201 | Detroit | Michigan |
| University of Nebraska Medical Center | 68198 | Omaha | Nebraska |
| NYU Longone Health (Long Island) | 11501 | Long Island City | New York |
| NYU Longone Health (Manhattan) | 10012 | Manhattan | New York |
| SCRI Oncology Partners | 37203 | Nashville | Tennessee |
| MD Anderson Cancer Center | 77030 | Houston | Texas |
| NEXT Oncology | 78229 | San Antonio | Texas |
| NEXT Virginia | 22031 | Fairfax | Virginia |
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