A Phase 1-2 Study of the Safety and Activity of ASTX029 in Patients with Advanced Solid Tumors

Phase 1

• Conditions: Advanced Solid Tumors; MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-004568-72-FR
• Lead Sponsor: Astex Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-11
• Last Update Posted: 21 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1) Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before any study-specific procedure is performed.
2) Men or women 18 years of age or older.
3) Subjects 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, subjects must also have documented gene alterations in the MAPK pathway as detailed in Section 4.1.2 and Table 2.
4) In Phase 1 Part B of the protocol, subjects must have disease lesions that are amenable to biopsy.
5) In the Phase 2 portion of the protocol, subjects must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
6) Eastern Cooperative Oncology Group performance status 0 to 2.
7) Acceptable organ function, as evidenced by the following laboratory data:
a) AST and alanine aminotransferase (ALT) =2×upper limit of normal (ULN) or =3 ULN in
the presence of liver metastases.
b) Total serum bilirubin =1.5×ULN.
c) Absolute neutrophil count (ANC) =1500 cells/mm3 .
d) Platelet count =100,000 cells/mm3 .
e) Calculated creatinine clearance (by the standard Cockcroft-Gault formula) of =50 mL/min or glomerular filtration rate of =50 mL/min.
8) 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 (urine or serum as required by local regulations) within 24 hours before the first dose of study treatment. Women of child-bearing potential must agree to the following during the treatment period and for 5 half-lives of ASTX029 or metabolite plus 30 days after receipt of the last dose of study treatment:
a) Refrain from donating eggs (ova, oocytes) for the purpose of reproduction.
b) Use a contraceptive method that is highly effective with a failure rate of <1% per year, with low user dependency. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk of inclusion of a woman with an early unexpected pregnancy.
9. Men must agree to the following during the treatment period and for 5 half-lives of ASTX029 or metabolite plus 90 days after receipt of last dose of study treatment:
a) Refrain from donating sperm.
b) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and to remain abstinent OR to use a male condom when having sexual intercourse with a woman of childbearing potential (according to recommendations of the CTFG; see protocol for details) who is not currently pregnant, and the 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 a condom may break or leak. The investigator should evaluate the effectiveness of the contraceptive method before the first dose of study treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

1) Hypersensitivity to ASTX029 or excipients of the drug product.
2) Poor medical risk in the investigator’s opinion because of systemic diseases in addition to the cancer under study, for example, uncontrolled infections.
3) 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 ASTX029.
4) Prior anticancer treatments or therapies within the indicated time window prior to first dose of study treatment (ASTX029), as follows:
a) 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.
b) Monoclonal antibodies or biologics within 4 weeks prior. Any encountered treatment related toxicities not stabilized or resolved to =Grade 1.
c) 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 (excepting alopecia) not stabilized or resolved to =Grade 1.
5) Prior treatment with ERK inhibitors.
6) History of, or at risk for, cardiac disease, as evidenced by 1 or more of the following conditions:
a) Abnormal left ventricular ejection fraction (LVEF; <50%) on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan.
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 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.
e) Screening 12-lead ECG with measurable QTc interval of =470 msec. (Fridericia's formula should be used to calculate the QTc interval throughout the study.)
7) 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.
8) Known brain metastases, unless previously treated and stable for at least 3 months with or without steroids.
9) 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.
10) History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including:
a) Presence of predisposing factors to RVO or CSR (eg, uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus) or
b) 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

Study & Design

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