first-in-human study of atx-295, an oral inhibitor of kif18a, in patients with advanced or metastatic solid tumors, including ovarian cancer

Conditions: Advanced Solid Tumors; Breast Cancer Recurrent; Ovarian Cancer; High-grade Serous Ovarian Carcinoma; Triple Negative Breast Cancer

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.

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

Keywords: kif kif18a hgsoc platinum-resistant platinum-intolerant platinum-refractory