Study of ASTX295 in Patients With Solid Tumors With Wild-Type p53

NCT03975387 | Terminated Phase 1 FDA Drug

• 2 other identifiers: ASTX295-012021-005033-16
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 11

Brief Summary

Study ASTX295-01 is a first in human Phase 1/2 open-label study of the safety, pharmacokinetics, and preliminary activity of ASTX295 in participants with wild-type TP53 advanced solid tumors. Phase 1 is a dose escalation and dose expansion study design. Sponsor made the strategic decision to not pursue the Phase 2 part of the study.

Conditions

Solid Tumor

Keywords

solid tumor; mesothelioma; TP53

Outcome Measures

Primary Outcomes (4)

• Phase 1a: Safety and tolerability of ASTX295 including determination of maximum tolerated dose (MTD), and/or recommended dose for expansion (RDE) to Phase 1b

  From the date of the first dose until 30 days after discontinuation of study treatment

• Phase 1b: Recommended Phase 2 dose (RP2D) and regimen of ASTX295 to proceed to Phase 2

  The RP2D will be based on incidence and severity of AEs, including SAEs and will be determined by the data and safety review committee (DSRC)

  From the date of the first dose until 30 days after discontinuation of study treatment, an average of 6 months to 1 year

• Phase 2: Disease control rate (DCR) in Cohort 1

  DCR will be calculated in Cohort 1 as the number of subjects whose response at Week 16 is CR, partial response (PR), or stable disease, divided by the total number of subjects evaluable for DCR analysis.

  From the date of the first dose until Week 16

• Phase 2: Overall response rate (ORR) in Cohorts 2, 3, 4, 5, and 6

  ORR in Cohorts 2, 3, 4, 5, and 6 will be calculated as the number of subjects whose best response is CR or PR, divided by the total number of subjects evaluable for ORR analysis.

  From the date of the first dose until study treatment discontinuation, an average of 6 months to 1 year

Secondary Outcomes (11)

• Phase 1: Preliminary clinical activity of ASTX295 as assessed by disease control rate (DCR)

  From the date of the first dose until Week 16

• Phase 1: Preliminary clinical activity as assessed by objective response rate (ORR) of ASTX295

  From the date of the first dose until study treatment discontinuation, an average of 6 months to 1 year

• Phase 2: Safety profile of ASTX295

  From the date of the first dose until 30 days after discontinuation of study treatment, an average of 6 months to 1 year

• Phase 2: Progression free survival (PFS)

  Up to approximately 1 year

• Phase 2: Overall survival (OS)

  Up to approximately 1 year

Study Arms (1)

ASTX295

EXPERIMENTAL

Drug: ASTX295

Interventions

ASTX295 DRUG

ASTX295 orally for 28-day cycle continuous or on an intermittent dosing schedule.

ASTX295

Eligibility Criteria

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

You may qualify if:

• Age
• Participant must be 18 years of age or older, at the time of signing the informed consent.
• Type of Participant and Disease Characteristics
• Have histologically or cytologically confirmed advanced solid tumors that are metastatic or unresectable and are refractory or have relapsed after treatment with standard available therapies or for whom standard life-prolonging measures are not available.
• Phase 1: any tumor type is eligible
• Phase 2: eligible tumor types as follows: malignant pleural mesothelioma (MPM) (Cohort 1); Liposarcoma (well-differentiated (WD) , de- differentiated (DD), or mix), intimal sarcoma, and other sarcomas with human murine double minute 2 (MDM2) amplification (Cohort 2); Glioblastoma multiforme (GBM) and tumors with CDNK2A loss of function (LOF) excluding MPM, liposarcoma, intimal sarcoma, and uveal melanoma (UVM) (Cohort 3); any solid tumors with molecular feature that may confer sensitivity to ASTX295 (Cohort 4); Uveal melanoma (Cohort 5); Any cancer type with MDM2 amplification excluding MPM, sarcoma, and UVM(Cohort 6).
• Documented wild-type TP53 and other molecular feature requirements.
• Have an Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 to 2.
• Acceptable bone marrow function, as evidenced by the following laboratory data:
• Absolute neutrophil count (ANC) ≥1500 cells/mm3
• Platelet count ≥100,000 cells/mm3
• Hemoglobin \>9 g/dL
• Adequate hepatic function as evidenced by:
• Serum total bilirubin ≤1.5 × upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (≤ 3 ULN in the presence of liver metastases).

You may not qualify if:

• Medical Conditions
• 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 subject safety, or the integrity of study outcomes, or interfere with the absorption or metabolism of ASTX295.
• History of, or at risk for, cardiac disease, as evidenced by any of the following conditions:
• Abnormal left ventricular ejection fraction.
• Congestive cardiac failure of ≥Grade 3.
• Unstable cardiac disease.
• History or evidence at Screening of long QT interval corrected for heart rate (QTcF), ventricular arrhythmias, clinically significant bradyarrhythmias, third-degree atrioventricular (AV) block, presence of cardiac pacemaker or defibrillator, or other clinically significant arrhythmias.
• Screening 12-lead electrocardiogram (ECG) with measurable QTcF interval of ≥470 msec. (Fridericia's formula should be used).
• Known advanced human immunodeficiency virus (HIV) infection (including AIDS): clinical stage ≥ 3 according to WHO classification and/or HIV-associated immunodeficiency.
• Known active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection (Inactive Hepatitis Carrier and subjects with laboratory evidence of no active replication on antivirals - viral load below limit of detection- will be permitted).
• Known brain metastases, unless previously treated and clinically stable for at least 4 weeks 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 subject to high risk of noncompliance with the protocol treatment or assessments.
• Prior/Concomitant Therapy
• Prior anticancer treatments or therapies within the indicated time window prior to first dose of study treatment (ASTX295), as follows:

Sponsors & Collaborators

• Taiho Oncology, Inc.: lead

Study Sites (11)

City of Hope Comprehensive Cancer Center Site#114

Duarte, California, 91010, United States

Location

Cedars-Sinai Medical Center Site #105

Los Angeles, California, 90048, United States

Location

Hoag Hospital Site#110

Newport Beach, California, 92663, United States

Location

Holden Comprehensive Cancer Center Site#108

Iowa City, Iowa, 52242, United States

Location

University of Michigan Rogel Cancer Center Site#109

Ann Arbor, Michigan, 48109, United States

Location

Regions Cancer Center Site #115

Saint Paul, Minnesota, 55101, United States

Location

Columbia University Irving Medical Center - Herbert Irving Pavilion Site#104

New York, New York, 10032, United States

Location

University of Pennsylvania-Abramson Cancer Center Site#113

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas MD Anderson Cancer Center Site #102

Houston, Texas, 77030, United States

Location

NEXT Oncology Site #101

San Antonio, Texas, 78229, United States

Location

Virgnia Cancer Specialists Site #103

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Mesothelioma

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Study Design

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

Study Record Dates

• First Submitted: May 28, 2019
• First Posted: June 5, 2019
• Study Start: July 11, 2019
• Primary Completion: September 11, 2023
• Study Completion: August 15, 2024
• Last Updated: April 9, 2025

Record last verified: 2025-04

Locations

US (11)