Study of ASTX029 in Subjects With Advanced Solid Tumors
NCT ID: NCT03520075
Last Updated: 2025-07-03
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1/PHASE2
192 participants
INTERVENTIONAL
2018-05-07
2025-03-03
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Phase 1A: Cohort 1 Dose Escalation
Participants received ASTX029 10 milligrams (mg), powder in bottle (PiB), orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.
ASTX029
PiB
Phase 1A: Cohort 2 Dose Escalation
Participants received ASTX029 20 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.
ASTX029
PiB
Phase 1A: Cohort 3 Dose Escalation
Participants received ASTX029 60 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.
ASTX029
PiB
Phase 1A: Cohort 4 Dose Escalation
Participants received ASTX029 120 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.
ASTX029
PiB
Phase 1A: Cohort 5 Dose Escalation
Participants received ASTX029 200 mg, orally, PiB, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.
ASTX029
PiB
Phase 1A: Cohort 6 Dose Escalation
Participants received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.
ASTX029
Tablet
Phase 1A: Cohort 7 Dose Escalation
Participants received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.
ASTX029
Tablet
Phase 1A: Cohort 8 Dose Escalation
Participants received ASTX029 40 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.
ASTX029
Tablet
Phase 1A: Cohort 9 Dose Escalation
Participants received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.
ASTX029
Tablet
Phase 1A: Cohort 10 Dose Escalation
Participants received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.
ASTX029
Tablet
Phase 1A: Cohort 11 Dose Escalation
Participants received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.
ASTX029
Tablet
Phase 1A: Cohort 12 Dose Escalation
Participants received ASTX029 280 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.
ASTX029
Tablet
Phase 1B Dose Expansion
Participants received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.
ASTX029
Tablet
Phase 2: Cohort A
Participants with neuroblastoma RAS (NRAS)-mutant melanoma received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.
ASTX029
Tablet
Phase 2: Cohort B
Participants with Kirsten RAS (KRAS)-mutant or KRAS-amplified non-small cell lung cancer (NSCLC) received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.
ASTX029
Tablet
Phase 2: Cohort C
Participants with B isoform of RAF kinase (BRAF) V600-mutant cancers (non-colorectal cancers) received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.
ASTX029
Tablet
Phase 2: Cohort D
Participants with BRAF-fusion cancers received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.
ASTX029
Tablet
Phase 2: Cohort E
Participants with gynecological cancers with alterations in the mitogen-activated protein kinase (MAPK) pathway received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.
ASTX029
Tablet
Phase 2: Cohort F
Participants with tumors that were characterized by other gene aberrations (that upregulate the MAPK signal pathway) received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.
ASTX029
Tablet
Interventions
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ASTX029
PiB
ASTX029
Tablet
Eligibility Criteria
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Inclusion Criteria
2. Men or women 18 years of age or older.
3. 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.
4. In Phase 1 Part B of the protocol, participants must have disease lesions that are amenable to biopsy.
5. In the Phase 2 portion of the protocol, participants must have measurable disease according to RECIST v1.1.
6. Eastern Cooperative Oncology Group performance status 0 to 2.
7. Acceptable organ function as evidenced by the following laboratory data:
1. Aspartate aminotransferase (AST) and alanine aminotransferase ≤2×upper limit of normal (ULN) or ≤3 ULN in the presence of liver metastases.
2. Total serum bilirubin ≤1.5×ULN.
3. Absolute neutrophil count (ANC) ≥1500 cells/mm3.
4. Platelet count ≥100,000 cells/mm3.
5. Calculated creatinine clearance (by the standard Cockcroft Gault formula) of ≥50 mL/min or glomerular filtration rate of ≥50 mL/min.
8. 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.
9. 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.
Exclusion Criteria
2. Poor medical risk in the investigator's opinion because of systemic diseases in addition to the cancer under study, for example, uncontrolled infections.
3. 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.
4. Prior anticancer treatments or therapies within the indicated time window prior to first dose of study treatment (ASTX029), as follows:
1. 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.
2. Monoclonal antibodies within 4 weeks prior. Any encountered treatment-related toxicities not stabilized or resolved to ≤Grade 1.
3. 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.
5. Prior treatment with extracellular signal-regulated kinase (ERK) inhibitors.
6. History of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:
1. Abnormal left ventricular ejection fraction (LVEF; \<50%) on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.
2. 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.
3. Unstable cardiac disease including unstable angina or hypertension as defined by the need for overnight hospital admission within the last 3 months (90 days).
4. 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.
5. 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.)
7. 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.
8. Known brain metastases, unless previously treated and stable for at least 3 months with or without steroids.
9. 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.
10. History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including:
1. Presence of predisposing factors to RVO or CSR (eg, uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus) or
2. 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.
18 Years
ALL
No
Sponsors
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Taiho Oncology, Inc.
INDUSTRY
Responsible Party
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Locations
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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
Clinica Universidad de Navarra Madrid Site #242
Madrid, , Spain
Clínica Universidad de Navarra Site#242
Madrid, , Spain
The Christie NHS Foundation Trust Site#220
Manchester, England, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
Cambridge, , United Kingdom
The Newcastle Upon Tyne Hospitals NHS Foundation Trust Site #221
Newcastle upon Tyne, , United Kingdom
Churchill Hospital Site #224
Oxford, , United Kingdom
Countries
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References
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Munck JM, Berdini V, Bevan L, Brothwood JL, Castro J, Courtin A, East C, Ferraldeschi R, Heightman TD, Hindley CJ, Kucia-Tran J, Lyons JF, Martins V, Muench S, Murray CW, Norton D, O'Reilly M, Reader M, Rees DC, Rich SJ, Richardson CJ, Shah AD, Stanczuk L, Thompson NT, Wilsher NE, Woolford AJ, Wallis NG. ASTX029, a Novel Dual-mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK. Mol Cancer Ther. 2021 Oct;20(10):1757-1768. doi: 10.1158/1535-7163.MCT-20-0909. Epub 2021 Jul 30.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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ASTX029-01
Identifier Type: -
Identifier Source: org_study_id
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