Evaluate Preliminary Anti-tumor Activity of Elraglusib in Adult Participants With Advanced Solid Tumors

Официальное название

Phase 1/2 Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Anti-Tumor Activity of Elraglusib Oral Tablets in Adult Participants With Advanced Solid Tumors.

Обзор

This study is being done to test the safety of elraglusib when taken once a day and to assess: * How the body processes the drug (pharmacokinetics) * Assess potential effects of the drug on heart rhythm * Find the highest daily dose that can be given without causing side effects

Подробное описание

The study is a Phase 1/2, open label, dose escalation, safety, PK, PD and antitumor activity study of elraglusib tablets in participants aged 18 years or older with a histologically or cytologically confirmed diagnosis of advanced metastatic or progressive malignant solid tumors who are intolerant of or the malignancy is refractory to established therapy know to provide clinical benefit for their condition, or the malignancy has relapsed after standard therapy. Participants must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 measured by computed tomography (CT) scan or MRI to be eligible.

The study's primary objective is to determine the MTD or MAD and DLTs of elraglusib tablets administered daily. The secondary objectives are to study the PK of elraglusib tablets, to evaluate preliminary antitumor activity of elraglusib when administered as tablets, and to establish the RDEs of elraglusib tablets in subsequent development.

Вмешательства

• Препарат Elraglusib Oral Tablets
  Elraglusib Oral Tablet, 250 mg

Первичные конечные точки

• To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and dose-limiting toxicities (DLTs) of elraglusib tablets [Срок оценки: Determined at the end of Cycle 1 (each cycle is 21/28days) for each dose group tested up to 24 moths.]

Вторичные конечные точки (11)

• Pharmacokinetic Assessment [Срок оценки: From date of first dose through completion of Initial 21-day cycle. (Assessed Cycle 1 Only-up to 28 days) for each dose cohort, up to 24 months.]
• Pharmacokinetic Assessment [Срок оценки: From date of first dose through completion of Initial 21-day cycle. (Assessed Cycle 1 Only-up to 28 days) for each dose cohort, up to 24 months.]
• Pharmacokinetic Assessment [Срок оценки: From date of first dose through completion of initial 21-day cycle. (Assessed Cycle 1 Only-up to 28 days) for each cohort, up to 24 months.]
• Pharmacodynamic Assessment [Срок оценки: From Day 1 Dosing through completion of Day 21 of Cycle 1 only. (Assessed Cycle 1 only, up to 28-days) for each dose cohort up to 24 months.]
• Pharmacodynamic Assessment [Срок оценки: From date of first dose through completion of Initial 21-day cycle. (Assessed Cycle 1 Only-up to 28 days) for each dose cohort, up to 24 months.]
• Pharmacodynamic Assessment [Срок оценки: From date of first dose through completion of Initial 21-day cycle. (Assessed Cycle 1 Only-up to 28 days) for each dose cohort, up to 24 months.]
• Tumor Assessments [Срок оценки: Baseline and per standard of care every 9 (±1) weeks during treatment and during follow-up through disease progression for unto 30 months.]
• Electrocardiogram (ECG) [Срок оценки: Participation will be from Date of Screening through completion of the End of Treatment Visit, (EoT Visit), for up to 30 months. (Phase 1 Only)]
• Electrocardiogram (ECG) [Срок оценки: Participation will be from Date of Screening through completion of the End of Treatment Visit, (EoT Visit), for up to 30 months. (Phase 1 Only)]
• Safety Assessments [Срок оценки: From date of randomization until 30 days after receiving their last dose of study drug/completion of the End of Treatment Visit for up to 30 months.]
• Number of participants with clinically significant changes in laboratory parameters, vital signs, and physical examinations. [Срок оценки: Participants will be tracked from Date of first dose through completion of end of study/Treatment visit for up to 30 months.]

Критерии участия

Критерии включения

• Participants must meet all of the following criteria to be eligible for inclusion in the study:

• Able to understand and voluntarily sign a written informed consent and is willing and able to comply with the protocol requirements including scheduled visits, treatment plan, laboratory tests and other study procedures
• Age ≥ 18 years
• Has histologically or cytologically confirmed diagnosis of advanced metastatic or progressive solid tumor characterized by one or more of the following:

• Participant is intolerant of existing therapy(ies) known to provide clinical benefit for their condition
• Malignancy is refractory to existing therapy(ies) known to potentially provide clinical benefit
• Malignancy has relapsed after standard therapy
• Participant has contraindication to or declines standard therapies
• Has at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, measured preferably by computed tomography (CT) scan or magnetic resonance image (MRI)
• Has laboratory function within specified parameters (may be repeated):

• Adequate bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L; hemoglobin ≥ 8.5 g/dL, platelets ≥ 100 x 103/μL
• Adequate liver function: transaminases (aspartate aminotransferase/ alanine aminotransferase, AST/ALT) and alkaline phosphatase ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x the ULN if liver metastases are present; total bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN if elevations are due to underlying disease or concomitant medication/diseases
• Adequate renal function: BSA-adjusted glomerular filtration rate (GFR) ≥ 60 mL/min determined by multiplying estimated GFR by participant's body surface area (BSA) and dividing by 1.73
• Eastern Co-operative Oncology Group (ECOG) Performance Status (PS) ≤ 2
• Women of childbearing potential must have a negative baseline blood or urine pregnancy test within 72 hours of first dose of study drug. Women may be neither breastfeeding nor intending to become pregnant during study participation and must agree to use effective contraceptive methods (hormonal or barrier method of birth control, or true abstinence) for the duration of study participation and in the following 6 months after discontinuation of study treatment
• Male participants with partners of childbearing potential must take appropriate precautions to avoid fathering a child from screening until 6 months after discontinuation of study treatment and use appropriate barrier contraception or true abstinence
• Must not be receiving any other investigational medicinal product

Критерии исключения

• Participants who meet any of the following criteria will be excluded from the study:

• Pregnant or lactating
• Known to be hypersensitive to any of the components of elraglusib tablets or to the excipients used in its formulation
• Has not recovered from clinically significant toxicities as a result of prior anticancer therapy, except alopecia and/or infertility. Recovery is defined as ≤ Grade 2 severity per Common Terminology Criteria for Adverse Events (CTCAE), v6.0
• The following risk factors for abnormal heart rhythms/QT prolongation:

• A history of Torsade de pointes (TdP), other ventricular arrhythmias, or long QT syndrome
• A QT or QT interval corrected using Fridericia's formula (QTcF) > 470 msec at Screening from triplicate ECGs
• Has significant cardiovascular impairment: congestive heart failure greater than New York Heart Association (NYHA) Class II, family history of long QT syndrome, unstable angina, or stroke within 6 months of the first dose of study therapy
• Has had a myocardial infarction within 6 months of the first dose of study therapy or has ECG abnormalities that are deemed medically relevant by the investigator
• Has symptomatic brain metastases or leptomeningeal involvement as assessed by CT scan or MRI. Participants with stable brain metastases or leptomeningeal disease are eligible provided they have not required new treatments for this disease in a 28-day period before the first dose of study drug, and anticonvulsants and steroids are at a stable dose for a period of 14 days prior to the first dose of study drug
• Has had major surgery within 14 days prior to study entry or is planned to have major surgery during the course of the study (major surgery may be defined as any invasive operative procedure in which an extensive resection is performed, e.g., a body cavity is entered, organs are removed, or normal anatomy is altered. In general, if a mesenchymal barrier is opened \[pleural cavity, peritoneum, meninges\], the surgery is considered major)
• Has any medical and/or social condition which, in the opinion of the Investigator or Medical Monitor would preclude study participation
• Previous anticancer therapies with any of the following:

• Small molecule ≤ 14 days or 5× the terminal phase elimination t1/2, whichever is shorter, prior to the first dose of study drug
• Cytotoxic chemotherapy ≤ 14 days prior to the first dose of study drug
• Treatment with biologics (e.g., monoclonal antibodies, bispecific antibodies, cancer vaccines) ≤14 days prior to the first dose of study drug
• Broad field radiation therapy ≤14 days prior to the first dose of study drug
• Focal radiation therapy (including palliative) ≤ 7 days prior to the first dose of study drug
• Systemic and topical corticosteroids ≤ 7 days prior to the first dose of study drug
• Use of sensitive substrates of CYP3A4 with a narrow therapeutic from 14 days prior to first administration of study drug, during the study, and until Safety Follow-up Visit.
• Use of strong inhibitors or inducers of CYP2C19, CYP1A2 and CYP3A4 from 14 days prior to first administration of study drug, during the study, and until Safety Follow-up Visit.
• Use of inhibitors or inducers of major drug transporters (i.e., OATP1B1, OATP1B3, OCT1, OCT2 and MATE1/2K) from 14 days prior to first administration of study drug, during the study, and until the Safety Follow-up Visit.
• Concomitant participation in another clinical study with study drug(s) or device
• Unable to swallow a tablet or has any condition(s) that, in the opinion of the treating investigator, may affect gastrointestinal absorption
• Considered to be a member of a vulnerable population (for example, prisoners)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07714395 · Actuate 2601

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗