Study ASTX295-01 is a first in human Phase 1/2 open-label study of the safety,
pharmacokinetics, and preliminary activity of ASTX295 in subjects with wild-type TP53
advanced solid tumors. Phase 1 is a dose escalation and dose expansion study design followed
by a Phase 2 study.
ASTX295 is a synthetic small molecule that acts as an antagonist of Murine Double Minute 2
(MDM2; human homolog also known as HDM2). Study ASTX295-01 is a Phase 1/2 first in human
(FIH) study with ASTX295 in subjects who are refractory or have relapsed after treatment with
standard of care therapies, or for whom standard life-prolonging measures or approved
therapies are not available.
Phase 1 is composed of Phase 1a and 1b, a dose escalation stage followed by a dose expansion
stage, respectively. Phase 1 is intended to identify the recommended dose for expansion (RDE)
and ultimately the recommended Phase 2 dose (RP2D).
1. Participant must be 18 years of age or older, at the time of signing the informed
Type of Participant and Disease Characteristics
2. 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
3. Documented wild-type TP53 gene status.
4. Have an Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 to 2.
5. Acceptable bone marrow function, as evidenced by the following laboratory data:
1. Absolute neutrophil count (ANC) ≥1500 cells/mm3
2. Platelet count ≥100,000 cells/mm3
3. Hemoglobin >9 g/dL
6. Adequate hepatic function as evidenced by:
1. Serum total bilirubin ≤1.5 × upper limit of normal (ULN).
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×upper
limit of normal (ULN) (≤ 3 ULN in the presence of liver metastases).
3. Serum creatinine ≤1.5 × ULN OR calculated creatinine clearance (by the standard
Cockcroft-Gault formula) of ≥50 mL/min or measured glomerular filtration rate of
7. Participant can be male or female
8. Capable of giving signed informed consent, which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol, and willing to participate in the study.
Participants are eligible to be included in Phase 1 Part B of the study only if all of
the following additional criteria apply:
9. In Phase 1 Part B (dose expansion) of the protocol, subjects must have disease lesions
that are amenable to biopsy and must agree and be able to undergo a pre- and on-
Participants are eligible to be included in Phase 2 of the study only if all of the
following additional criteria apply:
10. There is confirmed availability of sufficient tumor specimen either from archival
formalin-fixed, paraffin embedded (FFPE) tissue or tissue obtained by a fresh biopsy
for analyzing TP53 at a central laboratory.
1. Poor medical risk in the investigator's opinion because of systemic diseases in
addition to the cancer under study, for example, uncontrolled infections.
2. 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.
3. History of, or at risk for, cardiac disease, as evidenced by any of the following
1. Abnormal left ventricular ejection fraction.
2. Congestive cardiac failure of ≥Grade 3.
3. Unstable cardiac disease.
4. 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.
5. Screening 12-lead electrocardiogram (ECG) with measurable QTcF interval of ≥470
msec. (Fridericia's formula should be used).
4. Known advanced human immunodeficiency virus (HIV) infection (including AIDS): clinical
stage ≥ 3 according to WHO classification and/or HIV-associated immunodeficiency (CD4
count less than 500 per mm3 of blood). Antiretroviral therapy (ART) is allowed
(subjects should be on established ART for at least four weeks and have an HIV viral
load less than 400 copies/mL prior to enrollment).
5. 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).
6. Known brain metastases, unless previously treated and clinically stable for at least 4
weeks with or without steroids.
7. 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.
8. Prior anticancer treatments or therapies within the indicated time window prior to
first dose of study treatment (ASTX295), as follows:
1. Cytotoxic chemotherapy within 3 weeks prior. Any encountered treatment-related
toxicities (excepting alopecia) must be stabilized or resolved to ≤Grade 1.
2. Monoclonal antibodies, biologics, or immunotherapy within 4 weeks prior. Any
encountered treatment-related toxicities must be stabilized or resolved to ≤Grade
3. Molecularly targeted drug or other 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 must be stabilized or resolved to ≤Grade 1.
4. Major surgery or radiation within 4 weeks prior to first dose (palliative
radiotherapy to a single lesion within 2 weeks).
9. Prior treatment with MDM2 antagonist
10. Inability to swallow oral medication or inability or unwillingness to comply with the
administration requirements related to ASTX295.
Participants are excluded from the Phase 2 part of the study if any of the following
additional criteria apply:
11. Active malignancy other than the cancer under study (excludes low risk prostate
cancer, basal cell carcinoma of the skin and superficial bladder cancer).