A Study of HS-10504 in Patients With Advanced or Metastatic Non-Small-Cell Lung Cancer(NSCLC)

Официальное название

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-10504 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC）

Обзор

HS-10504 is a fourth-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR C797S mutation. This study will evaluate the safety, tolerability, pharmacokinetics and efficacy of HS-10504 in Chinese locally advanced or metastatic NSCLC.

Вмешательства

• Препарат HS-10504
  HS-10504 will be administered orally once daily in a continuous regimen. Participants will continue treatment until experiencing objective disease progression or meeting other protocol-specified criteria for discontinuation of study treatment.

Первичные конечные точки

• the maximum tolerated dose (MTD) or the maximum applicable dose (MAD) [Срок оценки: From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (21 days).]

Вторичные конечные точки (11)

• Incidence and severity of adverse events (AEs). [Срок оценки: From the first dose until 28 days after the last dose]
• maximum plasma concentration (Cmax) of HS-10504 (and its major matabolite) for the first dose and multiple dose adminitration of HS-10504 [Срок оценки: From the first dose until Circle 2 Day 1]
• Time to reach maximum plasma concentration (Tmax) for the first dose and multiple adminitration of HS-10504 (and its major matabolite) [Срок оценки: From the first dose until Circle 2 Day 1]
• half-life (T1/2) of HS-10504 (and its major matabolite) for the first dose and multiple dose adminitration of HS-10504 [Срок оценки: From the first dose until Circle 2 Day 1]
• Area under the curve (AUC) of HS-10504 (and its major matabolite) for the first dose and multiple dose adminitration of HS-10504 [Срок оценки: From the first dose until Circle 2 Day 1]
• Trough plasma concentration (Ctrough) of HS-10504 (and its major matabolite) [Срок оценки: From the first dose to disease progression or withdrawal from study, whichever came first, assessed up to 24 months]
• Objective response rate (ORR) [Срок оценки: up to 24 months]
• Disease Control Rate (DCR) [Срок оценки: up to 24 months]
• Duration of response (DOR) [Срок оценки: up to 24 months]
• Progression-free survival (PFS) [Срок оценки: From the first dose to disease progression or withdrawal from study, whichever came first, assessed up to 24 months]
• Overall survival (OS), only for dose-expansion stage subjects [Срок оценки: From the first dose up to death or withdrawal from study, whichever came first, assessed up to 24 months]

Критерии участия

Критерии включения

• Males or females, aged ≥ 18 years.
• Subjects with histologically or cytologically confirmed locally advanced or metastatic NSCLC
• Progressive disease on or after prior treatment with EGFR-TKIs.
• Enrollment will be restricted to participants with evidence of EGFR-positive in tumor as determined by local or central testing.
• At least 1 target lesion according to RECIST 1.1.
• ECOG PS score: 0-1.
• Estimated life expectancy> 12 weeks.
• Men or women should be using adequate contraceptive measures throughout the study.
• Women must have the evidence of non-childbearing potential.
• Signed and dated Informed Consent Form.

Критерии исключения

• Subjects with known oncogenic driver genes other than EGFR.
• Subjects with mixed cell histologic or with phenotypic transformation.
• Treatment with any of the following:

• Prior or concurrent treatment with fourth-generation EGFR tyrosine kinase inhibitors.
• Cytotoxic chemotherapy, any other investigational drugs, traditional Chinese medicine with anti-tumor indications, or other anti-tumor drugs within 14 days prior to the first dose of HS-10504 or require continued treatment with these drugs during the study.
• Any local radiotherapy 2 weeks prior to the first dose of study treatment; have received irradiation of more than 30% of bone marrow prior to the first dose
• Uncontrolled pleural effusion or ascites or pericardial effusion.
• Major surgery within 4 weeks before the first dose.
• CNS metastases with symptomatic or active progression.
• Subjects who have any grade ≥2 residual toxicities from prior therapies.
• Subjects who have history of other primary malignancies.
• Inadequate bone marrow reserve or hepatic and renal functions.
• Subjects with severe or poorly controlled diabetes, cardiovascular diseases or hypertension; subjects with severe arteriovenous thrombotic events, severe infection, clinically significant bleeding symptoms or clinically significant gastrointestinal dysfunction.
• Hypersensitivity to any ingredient of HS-10504.
• Moderate to severe pulmonary diseases.
• Prior history of significant neurological or mental disorders.
• Women who are breastfeeding or pregnant or planned to be pregnant during the study period.
• Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator.
• Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Guangzhou Medical University — Гуанчжоу

Идентификаторы

NCT: NCT06461156 · HS-10504-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗