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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 90
- 试验地点
- 10
- 主要终点
- Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of ATX-295
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Dose Expansion: Platinum-Resistant, -Refractory, or -Intolerant HGSOC
干预措施: ATX-295 (Drug)
Dose Escalation
Subjects will be enrolled at various doses and/or schedules of ATX-295 to identify the expansion dose(s) and RP2D
干预措施: ATX-295 (Drug)
结局指标
主要结局
Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of ATX-295
时间窗: 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)
时间窗: 12 months
Adverse events graded according to CTCAE v5.0
次要结局
- Preliminary evidence of antitumor activity(12 months)
- 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)