Advanced Solid Tumors, Breast Cancer Recurrent, High-grade Serous Ovarian Carcinoma, Ovarian Cancer, Triple Negative Breast Cancer
Conditions
Keywords
KIF, KIF18A, HGSOC, Platinum-resistant, Platinum-intolerant, Platinum-refractory
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.
Interventions
DRUGATX-295
ATX-295 Tablets will be taken orally
Sponsors
Accent Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) | 12 months | Adverse events graded according to CTCAE v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
United States
Contacts
CONTACTPriya Rajaratnam
STUDY_DIRECTORGozde Colak, PhD
339-707-5855
Outcome results
None listed