Clinical study to find out how safe is ASTX295 (study drug) and how ASTX295 affects the body in patients with advanced solid tumors with normal TP53 gene

Phase 1

• Conditions: Subjects with Wild-Type TP53 Advanced Solid Tumors; MedDRA version: 20.0Level: PTClassification code 10027406Term: MesotheliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10081431Term: Uveal melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-005033-16-IT
• Lead Sponsor: ASTEX PHARMACEUTICALS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-09-14
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 186

Inclusion Criteria

1) Participant must be 18 years of age or older, at the time of signing the informed consent.
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 available.
a. Phase 1: any tumor type is eligible
b. Phase 2: eligible tumor types are as follows:
i) MPM (Cohort 1)
ii) Liposarcoma (WD, DD, or mix), intimal sarcoma, and other sarcomas with MDM2 amplification (Cohort 2)
iii) GBM and tumors with CDNK2A LOF excluding MPM, liposarcoma, intimal sarcoma, and UVM (Cohort 3)
iv) Tumors with BRCA1/2 or ATM deleterious mutations or with BAP1 LOF excluding MPM, liposarcoma, intimal sarcoma, and UVM (Cohort 4)
v) Uveal melanoma (Cohort 5)
vi) Any cancer type with MDM2 amplification excluding MPM, sarcoma, and UVM (Cohort 6)
3) Wild-type TP53 and other molecular feature requirements.
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:
a. Absolute neutrophil count (ANC) =1500 cells/mm3
b. Platelet count =100,000 cells/mm3
c. Hemoglobin >9 g/dL
6) Adequate hepatic function as evidenced by:
a. Serum total bilirubin =1.5 × upper limit of normal (ULN).
b. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × ULN (=3 × ULN in the presence of liver metastases).
c. 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 =50 mL/min.
7) Participant can be male or female
a. Male participants: Male participants are eligible to participate if they agree to the following during the treatment period and for at least 93 days (approximately 5 half-lives of ASTX295 [additional details can be found in the ASTX295
IB] plus 90 days) after the last dose of study treatment:
• Refrain from donating sperm.
PLUS either:
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.
OR
• Must agree to use contraception/barrier as detailed below:
o Agree to use a male condom when having sexual intercourse with a woman of childbearing potential.
o Female partner should be advised of the benefit of using an additional highly effective contraceptive method (with a failure rate of <1% per year) as described in Appendix 2 (Section 10.2) as a condom may break or leak.
b. Female participants:
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
i) Is not a woman of childbearing potential (WOCBP)
OR
ii) Is a woman of childbearing potential and is using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, as described in Appendix 2 (Section 10.2 of the protocol) during the treatment period and for at least 93 days (approximately 5 half-lives of ASTX295 [additional details can be found in the ASTX295 IB] plus 90 days) after the last dose of study treatment and agrees not to donate eggs (ova, oocytes) for the
purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment.
iii) A woman of chi

Exclusion Criteria

1) Poor medical risk in the investigator's opinion because of systemic diseases in addition to the cancer under study, for example, uncontrolled infections.
Confidential Information 34 Amendment 4, 21 March 2022 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 conditions:
a. Abnormal left ventricular ejection fraction (LVEF; <50%) on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan at Screening.
b. Congestive cardiac failure of =Grade 3 severity according to New York Heart Association (NYHA) functional classification defined as patients with marked limitation of activity and who are comfortable only at rest.
c. Unstable cardiac disease including unstable angina or hypertension as defined by the need for overnight hospital admission within the last 3 months (90 days).
d. History or evidence at Screening of long QT interval corrected for heart rate (QTcF), ventricular arrhythmias including ventricular bigeminy, clinically significant bradyarrhythmias such as sick sinus syndrome, third-degree atrioventricular (AV) block, presence of cardiac pacemaker or defibrillator, or other clinically significant arrhythmias.
e. 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 World Health Organization (WHO) classification (WHO 2007) 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 4 weeks and have an HIV viral load less than 400 copies/mL prior to enrollment).
5) Known active hepatitis B virus (HBV) or active hepatitis C virus (HCV) infection (inactive hepatitis carrier status 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:
a. Cytotoxic chemotherapy within 3 weeks prior. Any encountered treatment-related toxicities (excepting alopecia) must be stabilized or resolved to =Grade 1.
b. Monoclonal antibodies, biologics, or immunotherapy within 4 weeks prior. Any encountered treatment-related toxicities must be stabilized or resolved to =Grade 1.
c. Molecularly targeted drug or other investigational drugs, with 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.
d. Major surgery or radiation within 4 weeks prior to first dose (palliative radiotherapy to a single lesion within 2 weeks).
9) Pri

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified