First-in-Human Study of ATX-295, an Oral Inhibitor of KIF18A, in Patients With Advanced or Metastatic Solid Tumors, Including Ovarian Cancer

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат ATX-295
  ATX-295 Tablets will be taken orally

Первичные конечные точки

• Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of ATX-295 [Срок оценки: 12 months]
• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [Срок оценки: 12 months]

Вторичные конечные точки (5)

• Preliminary evidence of antitumor activity [Срок оценки: 12 months]
• Measurement of phospho-histone H3 in pre- and post-treatment biopsies for a subset of participants (pharmacodynamic biomarker) [Срок оценки: 12 months]
• Maximum observed plasma concentration of ATX-295 (Cmax) [Срок оценки: 12 months]
• Calculated time to reach maximum observed plasma concentration (Tmax) [Срок оценки: 12 months]
• Calculated area under the plasma concentration-time curve of ATX-295 (AUC0-t) [Срок оценки: 12 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 6 центров

• Florida Cancer Specialists — Sarasota
• Karmanos Cancer Institute — Detroit
• SCRI Oncology Partners — Nashville
• MD Anderson Cancer Center — Houston
• NEXT Oncology — San Antonio
• NEXT Virginia — Fairfax

Идентификаторы

NCT: NCT06799065 · ATX-295-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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