Solid Tumor, AdultPhase 1/2NCT03520075
Study of ASTX029 in Subjects With Advanced Solid Tumors
A Phase 1/2 study testing ASTX029 in people with Solid Tumor, Adult, run by Taiho Oncology, Inc. at 31 sites in 4 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Adult
- What is being tested?
- ASTX029
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 31 sitesin 4 countries
- Study dates
- 7 May 2018to 3 Mar 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
31 sites in 4 countries.
31 sites in 4 countries
United States19 sites
University of Michigan Rogel Cancer Center Site #113
Ann Arbor, Michigan, 48109
The Sidney Kimmel Comprehensive Cancer Center Site#106
Baltimore, Maryland, 21231
Massachusetts General Hospital Site#103
Boston, Massachusetts, 02114
Dana Farber Cancer Institute Site#104
Boston, Massachusetts, 02215
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Virginia Cancer Specialists Site#102
Fairfax, Virginia, 22031
The University of Texas MD Anderson Cancer Center Site#111
Houston, Texas, 77030
Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Southern California Norris Comprehensive Cancer Center Site#114
Los Angeles, California, 90033
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute Site# 107
Los Angeles, California, 90048
Smilow Cancer Hospital at Yale New Haven Site#105
New Haven, Connecticut, 06510
Columbia University Irving Medical Center - Herbert Irving Pavilion Site#112
New York, New York, 10032
Hoag Memorial Hospital Site#115
Newport Beach, California, 92658
University of Pennsylvania-Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Providence Portland Medical Center Site #118
Portland, Oregon, 97223
Oregon Health and Science University Site #122
Portland, Oregon, 97239
University of California Davis Medical Center Site #121
Sacramento, California, 95817
START - South Texas Accelerated Research Therapeutics, LLC Site# 101
San Antonio, Texas, 78229
California Pacific Medical Center - Sutter Pacific Medical Center Site#117
San Francisco, California, 94115-2378
Spain6 sites
Institut Català d'Oncologia Badalona Site#240
Barcelona, 08028
Hospital Universitari Vall d'Hebrón Servicio de Oncología, Sala coordinación UITM Site#243
Barcelona, 08035
Hospital Universitari Germans Trias i Pujol
Barcelona, 08916
Hospital Universitario Dexeus Site#241
Barcelona, 8028
Clinica Universidad de Navarra Madrid Site #242
Madrid, 28027
Clínica Universidad de Navarra Site#242
Madrid, 28027
United Kingdom4 sites
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ
The Christie NHS Foundation Trust Site#220
Manchester, England, M20 4BX
The Newcastle Upon Tyne Hospitals NHS Foundation Trust Site #221
Newcastle upon Tyne, NE7 7DN
Churchill Hospital Site #224
Oxford, OX3 7LE
France2 sites
Centre Léon Bérard Service d'Oncologie Médicale Site#202
Lyon, Auvergne-Rhône-Alpes, 69373
Hôpital de la Timone Site #201
Marseille, 13005
About this study
Official title: A Phase 1-2 Study of the Safety, Pharmacokinetics, and Activity of ASTX029 in Subjects With Advanced Solid Tumors
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.
Read the detailed description
ASTX029 is a synthetic small molecule inhibitor of extracellular signal-regulated kinases (ERKs) 1/2. ASTX029 has not been previously evaluated in human participants. The Phase 1 portion of this study will assess safety and determine the maximum tolerated dose, the recommended Phase 2 dose (RP2D), and the recommended dosing regimen of ASTX029 administered orally. The Phase 2 portion will assess preliminary clinical activity in tumors characterized by gene aberrations in the mitogen-activated protein kinase (MAPK) signal pathway that may confer sensitivity to ASTX029.
- Conditions
- Solid Tumor, Adult
- Being tested
- ASTX029
- Keywords
- Neoplasms, Solid Tumors, Antineoplastic Agents, MAPK, ERK
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASTX029Drug
PiB
ASTX029Drug
Tablet
| Study group | Role | What they receive |
|---|---|---|
| Phase 1A: Cohort 1 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1A: Cohort 2 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1A: Cohort 3 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1A: Cohort 4 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1A: Cohort 5 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1A: Cohort 6 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1A: Cohort 7 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1A: Cohort 8 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1A: Cohort 9 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1A: Cohort 10 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1A: Cohort 11 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1A: Cohort 12 Dose Escalation | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 1B Dose Expansion | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 2: Cohort A | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 2: Cohort B | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 2: Cohort C | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 2: Cohort D | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 2: Cohort E | Experimental | 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. Receives: Drug: ASTX029 |
| Phase 2: Cohort F | Experimental | 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. Receives: Drug: ASTX029 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs were defined as adverse events (AEs) graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria that occurred during the first cycle of treatment and represented any 1 of the following: grade 4 thrombocytopenia of any duration; ≥grade 3 hematologic toxicity with complications (e.g., grade 3 thrombocytopenia with bleeding or transfusion requirement); febrile neutropenia of any duration or grade 4 neutropenia of 5 days or more duration; liver-associated abnormalities; ≥grade 2 eye disorders; symptomatic grade 2 cutaneous toxicities (including skin rash); any other ≥grade 3 nonhematologic AE except grade 3 nausea, vomiting, or diarrhea; Any event that, in the opinion of the Data and Safety Review Committee (DSRC), would suggest that further dose escalation would put subjects at unacceptable risk.
Measured: Cycle 1 (cycle length = 21 days)
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs are defined as events that first occurred or worsened on or after the date of the first dose of study treatment until 30 days after the last dose of study treatment or until the start of a posttreatment alternative anti-cancer treatment, whichever occurs first, with the following exceptions: events that occurred after 30 days beyond the last dose of study treatment or the start of a posttreatment alternative anti-cancer treatment will also be considered treatment-emergent if the events are both serious and related to the study treatment.
Measured: From first dose of study drug up to 30 days after last dose (Up to 74 months)
Phase 2: Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
The ORR was calculated as the number of evaluable participants whose best response was complete response (CR) or partial response (PR), divided by the total number of participants evaluable for ORR analysis. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Percentages were rounded off to the nearest single decimal place
Measured: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 74 months)
Secondary outcomes (27)
Phase 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of ASTX029
As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in Cycle 1 Day1 (C1D1), received 120 mg in Cycle 2 and Day 1 (C2D1) and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.
Measured: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of ASTX029
As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1 received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.
Measured: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of ASTX029
As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.
Measured: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Maximum Observed Plasma Concentration (Cmax) of ASTX029
As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.
Measured: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Minimum Plasma Concentration (Cmin) of ASTX029
As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11. Data for Cmin was calculated and analyzed for C2D1 only.
Measured: Pre-dose and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 2 (Cycle length = 21 days)
Phase 1: Time to Reach Maximum Concentration (Tmax) of ASTX029
As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.
Measured: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Elimination Half-Life (T1/2) of ASTX029
As per planned analysis, data for participants from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 participant who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.
Measured: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Effect of Food on AUC0-24 of ASTX029
The food effect was to be analyzed only for tablet dosage forms. The participants who were administered 80 mg and 120 mg tablets, under both fed and fasted conditions were reported. As 200 mg dose was administered, as tablets, only under fasted conditions, hence food effect was not assessed for 200 mg dose. The statistical comparison between fed and fasted state treatment arm groups of 80 mg and 120 mg doses is reported in this outcome measure for food effect. The 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10.
Measured: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Effect of Food on AUC0-inf of ASTX029
The food effect was to be analyzed only for tablet dosage forms. The participants who were administered 80 mg and 120 mg tablets, under both fed and fasted conditions were reported. As 200 mg dose was administered, as tablets, only under fasted conditions, hence food effect was not assessed for 200 mg dose. The statistical comparison between fed and fasted state treatment arm groups of 80 mg and 120 mg doses is reported in this outcome measure for food effect. The 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10.
Measured: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Effect of Food on Cmax of ASTX029
The food effect was to be analyzed only for tablet dosage forms. The participants who were administered 80 mg and 120 mg tablets, under both fed and fasted conditions were reported. As 200 mg dose was administered, as tablets, only under fasted conditions, hence food effect was not assessed for 200 mg dose. The statistical comparison between fed and fasted state treatment arm groups of 80 mg and 120 mg doses is reported in this outcome measure for food effect. The 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10.
Measured: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Effect of Food on Tmax of ASTX029
The food effect was to be analyzed only for tablet dosage forms. The participants who were administered 80 mg and 120 mg tablets, under both fed and fasted conditions were reported. As 200 mg dose was administered, as tablets, only under fasted conditions, hence food effect was not assessed for 200 mg dose. The statistical comparison between fed and fasted state treatment arm groups of 80 mg and 120 mg doses is reported in this outcome measure for food effect. The 2 participants who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10.
Measured: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Inhibition of Phosphorylated Ribosomal S6 Kinase (pRSK) Protein in Response to ASTX029 Treatment in Tumor Biopsies as Assessed by H Score
The protein expression level is quantified through the H-score, calculated from staining intensity within the target cell region. H-Score = (3x % of cells with staining graded 3) + (2x % of cells with staining graded 2) + % of cells with staining graded 1. H-Score ranges between 0 to 300. The H-score is for sum of cytoplasmic H-Score (C pRSK H-Score) and nuclear H-Scores (N pRSK H-Score). C pRSK H-Scores, and nuclear H-Scores were combined to give a single H-score.
Measured: 4 hours post-dose on Day 8 of Cycle 2 (Cycle length = 21 days)
Phase 1: Progression Free Survival (PFS)
The PFS was defined as the number of months from the start of the study treatment to disease progression or death, whichever occurs first. The PFS was analyzed using a Kaplan-Meier method, with PFS time being censored on the date of the last disease assessment. The 90% CI for median PFS was provided using the Kaplan-Meier procedure.
Measured: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Phase 1: Overall Survival (OS)
The OS was defined as the number of months from the day the participant was randomized to the date of death (regardless of cause). Participants without a documented death date were censored on the last date they were known to be alive. The OS was presented using a Kaplan-Meier estimate.
The 90% CI for median OS was provided using the Kaplan-Meier procedure.
Measured: Up to 82 months
Phase 1: Disease Control Rate (DCR)
DCR was calculated as the number of participants whose best response was CR, PR, or stable disease (SD), divided by the total number of participants evaluable for DCR analysis. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. Percentages were rounded off to the nearest single decimal place.
Measured: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Phase 1: Duration of Response (DoR)
Duration of response was calculated for all responders from the date of the earliest assessment of CR or PR to the date of relapse or death, whichever occurred earlier, or the last disease assessment date for participants without a relapse or death. Duration of SD was calculated for participants whose best response is CR, PR, or SD from the day study drug was first taken to the date of disease progression or death, whichever occurred earlier, or the last disease assessment for participants without disease progression or death.
Measured: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Phase 2: AUC0-24 of ASTX029
Measured: Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1, 2, 4, and 8 hours post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)
Phase 2: AUC0-last of ASTX029
Measured: Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1, 2, 4, and 8 hours post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)
Phase 2: AUC0-inf of ASTX029
Data for Auc0-inf was collected and analyzed for C1D1 only.
Measured: Pre-dose on Day 1 of Cycle 1; and at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1 (Cycle length = 21 days)
Phase 2: Cmax of ASTX029
Measured: Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1, 2, 4, and 8 hours post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)
Phase 2: Cmin of ASTX029
Data for Cmin was calculated and analyzed for C3D1 only.
Measured: Pre-dose on Day 1 of Cycle 3; and at 0.5,1, 2, 4, and 8 post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)
Phase 2: Tmax of ASTX029
Measured: Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1, 2, 4, and 8 hours post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)
Phase 2: T1/2 of ASTX029
Data for T1/2 was collected and analyzed for C1D1 only.
Measured: Pre-dose on Day 1 of Cycle 1; at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1 (Cycle length = 21 days)
Phase 2: Progression Free Survival
The PFS was defined as the number of months from the start of the study treatment to disease progression or death, whichever occurs first. The PFS was analyzed using a Kaplan-Meier method, with PFS time being censored on the date of the last disease assessment. The 90% CI for median PFS was provided using the Kaplan-Meier procedure.
Measured: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Phase 2: Overall Survival
The OS was defined as the number of months from the day the participant was randomized to the date of death (regardless of cause). Participants without a documented death date were censored on the last date they were known to be alive. The OS was presented using a KM estimate. The 90% CI for median OS was provided using the Kaplan-Meier procedure.
Measured: Up to 82 months
Phase 2: Disease Control Rate
DCR was calculated as the number of participants whose best response was CR, PR, or SD, divided by the total number of participants evaluable for DCR analysis. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Phase 2: Duration of Response
Duration of response was calculated for all responders from the date of the earliest assessment of CR or PR to the date of relapse or death, whichever occurred earlier, or the last disease assessment date for participants without a relapse or death. Duration of SD was calculated for participants whose best response is CR, PR, or SD from the day study drug was first taken to the date of disease progression or death, whichever occurred earlier, or the last disease assessment for participants without disease progression or death.
Measured: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2018
- Study start7 May 2018
- Primary completion1 Aug 2024
- Study completion3 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid Tumor, AdultStudies of the same condition, open and under way.
- More trials run by Taiho Oncology, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taiho Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03520075
- Sponsor's protocol ID
- ASTX029-01
- Status last verified
- Jun 2025
- First submitted
- 18 Apr 2018
- Last updated
- 3 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 34330842
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1-2 Study of the Safety, Pharmacokinetics, and Activity of ASTX029 in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03520075
- Acronym / sponsor ID
- ASTX029-01
- Conditions
- Solid Tumor, Adult
- Keywords
- Neoplasms, Solid Tumors, Antineoplastic Agents, MAPK, ERK
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Taiho Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- 7 May 2018 (actual)
- Primary completion
- 1 Aug 2024 (actual)
- Study completion
- 3 Mar 2025 (actual)
- First posted
- 9 May 2018 (actual)
- Results
- Posted 3 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
ASTX029 is a synthetic small molecule inhibitor of extracellular signal-regulated kinases (ERKs) 1/2. ASTX029 has not been previously evaluated in human participants. The Phase 1 portion of this study will assess safety and determine the maximum tolerated dose, the recommended Phase 2 dose (RP2D), and the recommended dosing regimen of ASTX029 administered orally. The Phase 2 portion will assess preliminary clinical activity in tumors characterized by gene aberrations in the mitogen-activated protein kinase (MAPK) signal pathway that may confer sensitivity to ASTX029.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 19
| Arm | Type | Receives |
|---|---|---|
| Phase 1A: Cohort 1 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1A: Cohort 2 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1A: Cohort 3 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1A: Cohort 4 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1A: Cohort 5 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1A: Cohort 6 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1A: Cohort 7 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1A: Cohort 8 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1A: Cohort 9 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1A: Cohort 10 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1A: Cohort 11 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1A: Cohort 12 Dose Escalation | Experimental | Drug: ASTX029Participants 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. |
| Phase 1B Dose Expansion | Experimental | Drug: ASTX029Participants 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. |
| Phase 2: Cohort A | Experimental | Drug: ASTX029Participants 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. |
| Phase 2: Cohort B | Experimental | Drug: ASTX029Participants 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. |
| Phase 2: Cohort C | Experimental | Drug: ASTX029Participants 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. |
| Phase 2: Cohort D | Experimental | Drug: ASTX029Participants 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. |
| Phase 2: Cohort E | Experimental | Drug: ASTX029Participants 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. |
| Phase 2: Cohort F | Experimental | Drug: ASTX029Participants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (23 listed)
- 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:
- Prior treatment with extracellular signal-regulated kinase (ERK) inhibitors.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ASTX029PiB | Drug | Phase 1A: Cohort 1 Dose Escalation, Phase 1A: Cohort 2 Dose Escalation, Phase 1A: Cohort 3 Dose Escalation, Phase 1A: Cohort 4 Dose Escalation, Phase 1A: Cohort 5 Dose Escalation |
| ASTX029Tablet | Drug | Phase 1A: Cohort 10 Dose Escalation, Phase 1A: Cohort 11 Dose Escalation, Phase 1A: Cohort 12 Dose Escalation, Phase 1A: Cohort 6 Dose Escalation, Phase 1A: Cohort 7 Dose Escalation, Phase 1A: Cohort 8 Dose Escalation, Phase 1A: Cohort 9 Dose Escalation, Phase 1B Dose Expansion, Phase 2: Cohort A, Phase 2: Cohort B, Phase 2: Cohort C, Phase 2: Cohort D, Phase 2: Cohort E, Phase 2: Cohort F |
Primary outcome
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Cycle 1 (cycle length = 21 days)
DLTs were defined as adverse events (AEs) graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria that occurred during the first cycle of treatment and represented any 1 of the following: grade 4 thrombocytopenia of any duration; ≥grade 3 hematologic toxicity with complications (e.g., grade 3 thrombocytopenia with bleeding or transfusion requirement); febrile neutropenia of any duration or grade 4 neutropenia of 5 days or more duration; liver-associated abnormalities; ≥grade 2 eye disorders; symptomatic grade 2 cutaneous toxicities (including skin rash); any other ≥grade 3 nonhematologic AE except grade 3 nausea, vomiting, or diarrhea; Any event that, in the opinion of the Data and Safety Review Committee (DSRC), would suggest that further dose escalation would put subjects at unacceptable risk.
Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: From first dose of study drug up to 30 days after last dose (Up to 74 months)
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs are defined as events that first occurred or worsened on or after the date of the first dose of study treatment until 30 days after the last dose of study treatment or until the start of a posttreatment alternative anti-cancer treatment, whichever occurs first, with the following exceptions: events that occurred after 30 days beyond the last dose of study treatment or the start of a posttreatment alternative anti-cancer treatment will also be considered treatment-emergent if the events are both serious and related to the study treatment.
Phase 2: Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 74 months)
The ORR was calculated as the number of evaluable participants whose best response was complete response (CR) or partial response (PR), divided by the total number of participants evaluable for ORR analysis. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Percentages were rounded off to the nearest single decimal place
27 secondary outcomes
Phase 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Maximum Observed Plasma Concentration (Cmax) of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Minimum Plasma Concentration (Cmin) of ASTX029
Time frame: Pre-dose and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 2 (Cycle length = 21 days)
Phase 1: Time to Reach Maximum Concentration (Tmax) of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Elimination Half-Life (T1/2) of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Effect of Food on AUC0-24 of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Effect of Food on AUC0-inf of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Effect of Food on Cmax of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Effect of Food on Tmax of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)
Phase 1: Inhibition of Phosphorylated Ribosomal S6 Kinase (pRSK) Protein in Response to ASTX029 Treatment in Tumor Biopsies as Assessed by H Score
Time frame: 4 hours post-dose on Day 8 of Cycle 2 (Cycle length = 21 days)
Phase 1: Progression Free Survival (PFS)
Time frame: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Phase 1: Overall Survival (OS)
Time frame: Up to 82 months
Phase 1: Disease Control Rate (DCR)
Time frame: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Phase 1: Duration of Response (DoR)
Time frame: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Phase 2: AUC0-24 of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1, 2, 4, and 8 hours post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)
Phase 2: AUC0-last of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1, 2, 4, and 8 hours post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)
Phase 2: AUC0-inf of ASTX029
Time frame: Pre-dose on Day 1 of Cycle 1; and at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1 (Cycle length = 21 days)
Phase 2: Cmax of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1, 2, 4, and 8 hours post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)
Phase 2: Cmin of ASTX029
Time frame: Pre-dose on Day 1 of Cycle 3; and at 0.5,1, 2, 4, and 8 post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)
Phase 2: Tmax of ASTX029
Time frame: Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1, 2, 4, and 8 hours post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)
Phase 2: T1/2 of ASTX029
Time frame: Pre-dose on Day 1 of Cycle 1; at 0.5,1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 1 (Cycle length = 21 days)
Phase 2: Progression Free Survival
Time frame: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Phase 2: Overall Survival
Time frame: Up to 82 months
Phase 2: Disease Control Rate
Time frame: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Phase 2: Duration of Response
Time frame: Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34330842Munck 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
31 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ASTX029 in people with Solid Tumor, Adult, run by Taiho Oncology, Inc. at 31 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in United States, Spain, United Kingdom, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Cycle 1 (cycle length = 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03520075, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jul 2025.