Study of ASTX029 in Subjects With Advanced Solid Tumors

NCT03520075 | Completed Phase 1 Results FDA Drug

• 1 other identifier: ASTX029-01
• Study Type: interventional
• Target: 192
• Locations: 4 countries
• Sites: 31

Brief 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.

Conditions

Solid Tumor, Adult

Keywords

Neoplasms; Solid Tumors; Antineoplastic Agents; MAPK; ERK

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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

  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

  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

  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

  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

  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

  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)

Study Arms (19)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Drug: ASTX029

Interventions

ASTX029 DRUG

PiB

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (31)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

University of Southern California Norris Comprehensive Cancer Center Site#114

Los Angeles, California, 90033, United States

Location

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute Site# 107

Los Angeles, California, 90048, United States

Location

Hoag Memorial Hospital Site#115

Newport Beach, California, 92658, United States

Location

University of California Davis Medical Center Site #121

Sacramento, California, 95817, United States

Location

California Pacific Medical Center - Sutter Pacific Medical Center Site#117

San Francisco, California, 94115-2378, United States

Location

Smilow Cancer Hospital at Yale New Haven Site#105

New Haven, Connecticut, 06510, United States

Location

Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

The Sidney Kimmel Comprehensive Cancer Center Site#106

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital Site#103

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute Site#104

Boston, Massachusetts, 02215, United States

Location

University of Michigan Rogel Cancer Center Site #113

Ann Arbor, Michigan, 48109, United States

Location

Columbia University Irving Medical Center - Herbert Irving Pavilion Site#112

New York, New York, 10032, United States

Location

Providence Portland Medical Center Site #118

Portland, Oregon, 97223, United States

Location

Oregon Health and Science University Site #122

Portland, Oregon, 97239, United States

Location

University of Pennsylvania-Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas MD Anderson Cancer Center Site#111

Houston, Texas, 77030, United States

Location

START - South Texas Accelerated Research Therapeutics, LLC Site# 101

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists Site#102

Fairfax, Virginia, 22031, United States

Location

Centre Léon Bérard Service d'Oncologie Médicale Site#202

Lyon, Auvergne-Rhône-Alpes, 69373, France

Location

Hôpital de la Timone Site #201

Marseille, 13005, France

Location

Institut Català d'Oncologia Badalona Site#240

Barcelona, 08028, Spain

Location

Hospital Universitari Vall d'Hebrón Servicio de Oncología, Sala coordinación UITM Site#243

Barcelona, 08035, Spain

Location

Hospital Universitari Germans Trias i Pujol

Barcelona, 08916, Spain

Location

Hospital Universitario Dexeus Site#241

Barcelona, 8028, Spain

Location

Clinica Universidad de Navarra Madrid Site #242

Madrid, 28027, Spain

Location

Clínica Universidad de Navarra Site#242

Madrid, 28027, Spain

Location

The Christie NHS Foundation Trust Site#220

Manchester, England, M20 4BX, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust Site #221

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Churchill Hospital Site #224

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34330842 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

ASTX029

Limitations and Caveats

The ASTX029 clinical development program was terminated by the sponsor due to the changing treatment landscape.

Results Point of Contact

• Title: Taiho
• Organization: Taiho Oncology, Inc

clinicaltrialinfo@taihooncology.com

609-250-7336

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2018
• First Posted: May 9, 2018
• Study Start: May 7, 2018
• Primary Completion: August 1, 2024
• Study Completion: March 3, 2025
• Last Updated: July 3, 2025
• Results First Posted: July 3, 2025

Record last verified: 2025-06

Locations

FR (2); US (19); ES (6); GB (4)