Study of ASTX029 in Subjects With Advanced Solid Tumors

Completed · Phase 1/Phase 2

Conditions studied: Solid Tumor, Adult

In brief

This study is a first-in-human, open-label, multicenter, Phase 1-2 study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of ASTX029 administered orally to participants with advanced solid malignancies who are not candidates for approved or available therapies.

Key facts

Study ID

NCT03520075

Run by

Taiho Oncology, Inc.

People needed

192

Starts

2018-05-07

Expected to finish

2025-03-03

Last updated by the study team

2025-07-03

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must fulfill all of the following inclusion criteria.
• Able to understand and comply with study procedures, understand the risks involved in the study, and provide written informed consent before any study-specific procedure is performed.
• Men or women 18 years of age or older.
• Participants with histologically or cytologically confirmed advanced solid tumors that are metastatic or unresectable, who are refractory or have relapsed after treatment with available therapies or for whom standard life-prolonging measures or approved therapies are not available. In Phase 1 Part B and in the Phase 2 portion of the protocol, participants must also have documented gene alterations in the MAPK pathway as detailed in the protocol.
• In Phase 1 Part B of the protocol, participants must have disease lesions that are amenable to biopsy.
• In the Phase 2 portion of the protocol, participants must have measurable disease according to RECIST v1.1.
• Eastern Cooperative Oncology Group performance status 0 to 2.
• Acceptable organ function as evidenced by the following laboratory data:
• Aspartate aminotransferase (AST) and alanine aminotransferase ≤2×upper limit of normal (ULN) or ≤3 ULN in the presence of liver metastases.
• Total serum bilirubin ≤1.5×ULN.
• Absolute neutrophil count (ANC) ≥1500 cells/mm3.
• Platelet count ≥100,000 cells/mm3.
• Calculated creatinine clearance (by the standard Cockcroft Gault formula) of ≥50 mL/min or glomerular filtration rate of ≥50 mL/min.
• Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG]; see protocol for details) must not be pregnant or breastfeeding and must have a negative pregnancy test within 24 hours before the first dose of study treatment. While receiving study treatment and for at least 5 half-lives of ASTX029 or metabolite plus 30 days after completing treatment, women of child-bearing potential must agree to practice highly effective contraceptive measures (as described in the protocol) and must refrain from donating eggs (ova, oocytes) for the purpose of reproduction.
• Men with female partners of child-bearing potential (according to recommendations of the CTFG; see protocol for details) must agree to, during the treatment period and for at least 5 half-lives of ASTX029 or metabolite plus 90 days after completing treatment, practice highly effective contraceptive measures (as described in the protocol), not to father a child, and to refrain from donating sperm.

You may not qualify if…

• Hypersensitivity to ASTX029 or excipients of the drug product.
• Poor medical risk in the investigator's opinion because of systemic diseases in addition to the cancer under study, for example, uncontrolled infections.
• Life-threatening illness, significant organ system dysfunction, or other condition that, in the investigator's opinion, could compromise participants safety or the integrity of study outcomes or interfere with the absorption or metabolism of ASTX029.
• Prior anticancer treatments or therapies within the indicated time window prior to first dose of study treatment (ASTX029), as follows:
• Cytotoxic chemotherapy or radiotherapy within 3 weeks prior. Palliative radiotherapy to a single lesion within 2 weeks prior. Any encountered treatment-related toxicities (excepting alopecia) not stabilized or resolved to ≤Grade 1.
• Monoclonal antibodies within 4 weeks prior. Any encountered treatment-related toxicities not stabilized or resolved to ≤Grade 1.
• Molecularly targeted drug or investigational drugs, without the potential for delayed toxicity, within 4 weeks of the first dose of study treatment or 5 half-lives (minimum 14 days), whichever is shorter. Any encountered treatment-related toxicities (excepting alopecia) not stabilized or resolved to ≤Grade 1.
• Prior treatment with extracellular signal-regulated kinase (ERK) inhibitors.
• History of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:
• Abnormal left ventricular ejection fraction (LVEF; <50%) on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.
• Congestive cardiac failure of ≥Grade 3 severity according to New York Heart Association functional classification defined as patients with marked limitation of activity and who are comfortable only at rest.
• Unstable cardiac disease including unstable angina or hypertension as defined by the need for overnight hospital admission within the last 3 months (90 days).
• History or evidence of long QT interval corrected for heart rate (QTc), ventricular arrhythmias including ventricular bigeminy, complete left bundle branch block, clinically significant bradyarrhythmias such as sick sinus syndrome, second- and third-degree atrioventricular (AV) block, presence of cardiac pacemaker or defibrillator, or other significant arrhythmias.
• Screening 12-lead electrocardiogram (ECG) with measurable QTc interval of ≥470 msec. (Fridericia's formula should be used to calculate the QTc interval throughout the study.)
• Known history of human immunodeficiency virus (HIV) infection or seropositive results consistent with active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection.
• Known brain metastases, unless previously treated and stable for at least 3 months with or without steroids.
• Known significant mental illness or other conditions, such as active alcohol or other substance abuse that, in the opinion of the investigator, predispose the participant to high risk of noncompliance with the protocol treatment or assessments.
• History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including:
• Presence of predisposing factors to RVO or CSR (eg, uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus) or
• Visible retinal pathology as assessed by ophthalmic examination at screening that is considered a risk factor for RVO or CSR such as:
• Evidence of optic disc cupping or
• Evidence of new visual field defects on automated perimetry or
• Intraocular pressure >21 mmHg as measured by tonography.

Where it is running

• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• University of Southern California Norris Comprehensive Cancer Center Site#114 — Los Angeles, California, United States
• Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute Site# 107 — Los Angeles, California, United States
• Hoag Memorial Hospital Site#115 — Newport Beach, California, United States
• University of California Davis Medical Center Site #121 — Sacramento, California, United States
• California Pacific Medical Center - Sutter Pacific Medical Center Site#117 — San Francisco, California, United States
• Smilow Cancer Hospital at Yale New Haven Site#105 — New Haven, Connecticut, United States
• Holden Comprehensive Cancer Center — Iowa City, Iowa, United States
• The Sidney Kimmel Comprehensive Cancer Center Site#106 — Baltimore, Maryland, United States
• Massachusetts General Hospital Site#103 — Boston, Massachusetts, United States
• Dana Farber Cancer Institute Site#104 — Boston, Massachusetts, United States
• University of Michigan Rogel Cancer Center Site #113 — Ann Arbor, Michigan, United States
• Columbia University Irving Medical Center - Herbert Irving Pavilion Site#112 — New York, New York, United States
• Providence Portland Medical Center Site #118 — Portland, Oregon, United States
• Oregon Health and Science University Site #122 — Portland, Oregon, United States
• University of Pennsylvania-Abramson Cancer Center — Philadelphia, Pennsylvania, United States
• The University of Texas MD Anderson Cancer Center Site#111 — Houston, Texas, United States
• START - South Texas Accelerated Research Therapeutics, LLC Site# 101 — San Antonio, Texas, United States
• Virginia Cancer Specialists Site#102 — Fairfax, Virginia, United States
• Centre Léon Bérard Service d'Oncologie Médicale Site#202 — Lyon, Auvergne-Rhône-Alpes, France
• Hôpital de la Timone Site #201 — Marseille, France
• Institut Català d'Oncologia Badalona Site#240 — Barcelona, Spain
• Hospital Universitari Vall d'Hebrón Servicio de Oncología, Sala coordinación UITM Site#243 — Barcelona, Spain
• Hospital Universitari Germans Trias i Pujol — Barcelona, Spain
• Hospital Universitario Dexeus Site#241 — Barcelona, Spain

Full record on ClinicalTrials.gov

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