MC# 22-37 - A Phase I/IIa, Open-Label, Safety, Pharmacokinetic, and Preliminary Efficacy Study of Oral ATRN-119 in Patients with Advanced Solid Tumors
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Agent(s): ATRN-119
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Disease Type(s): Solid Tumor, Merkel Cell
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Phase(s): I, II
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Drug Classification(s): Small Molecule, Targeted Therapy
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Molecular Target(s): ATR
Mechanism of Action
ATRN-119 selectively targets and binds to ATR, and inhibits its activity and ATR-mediated signaling. This blocks the downstream phosphorylation of the serine/threonine protein kinase checkpoint kinase 1 (CHK1). This results in the inhibition of DNA damage checkpoint activation, the disruption of DNA damage repair, and the induction of tumor cell apoptosis.
Purpose
In this study, the sponsor and investigators want to learn:
- How much of ATRN-119 can be given with an acceptable level of side effects
- The effects of ATRN-119 (good and bad)
- How much of ATRN-119 is absorbed into the blood and how fast it is removed
- How much the tumor shrinks or grows in response to ATRN-119
Inclusion Criteria
- DNA damage response (DDR) mutations documented in the past medical record or confirmed during the screening period.
- Measurable disease defined by RECIST 1.1.
- Life expectancy ≥ 3 months.
- Subject must be capable of oral administration of study medication.
- Your study team will discuss all other inclusion criteria that apply to you.
Exclusion Criteria
- Subject has had a cytotoxic chemotherapy, immunotherapy, radiotherapy or other targeted therapies within 4 weeks (washout period may be different depending on the specific treatment).
- Surgical procedure performed within 7 days prior to first scheduled dose of ATRN-119.
- Concomitant treatment with strong inhibitors or inducers of CYP3A4 and CYP2D6.
- Known human immunodeficiency virus infection (HIV).
- Subjects with active viral or bacterial infections and/or receiving systemic antibiotics or anti-viral medications.
- Current or past diagnosis of leukemia within the past 5 years.
- Prior radiotherapy at the target lesion unless there is evidence of disease progression.
- Known CNS metastases or clinical evidence of CNS involvement that is not stable for previous 1 month by radiology documentation (magnetic resonance imaging [MRI] brain).
- History of non-malignant gastronintestinal (GI) bleeding, gastric stress ulcerations, or peptic ulcer disease within the past 3-months.
- Patient has uncontrolled hypertension at time of enrollment.
- Complete left bundle branch block (LBBB), bifascicular block (right bundle branch block [RBBB] with either left anterior hemiblock or left posterior hemiblock).
- Any clinically significant ST segment and/or T-wave abnormalities.
- Myocardial infarction or unstable angina pectoris within 6 months prior to starting study medication.
- Your study team will discuss all other exclusion criteria that apply to you.
Location
- Dallas, TX - Mary Crowley Cancer Research - Medical City
