A Study to Assess the Efficacy and Safety of WSD0922-FU in Patients With EGFRm+ Advanced Non-small Cell Lung Cancer

Официальное название

A Phase I/II Multicenter, Open Label, Single-arm Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of WSD0922-FU in the Treatment of Advanced Non-small Cell Lung Cancer

Обзор

This study is a multicenter, open label, single-arm phase I/II clinical trial of WSD0922-FU for patients with locally advanced or metastatic non-small cell lung cancer whose disease has progressed with thrid-generation EGFR-TKI .

Подробное описание

WSD0922-FU is a potent reversible inhibitor of both the single EGFRm+ and dual EGFRm+/C797S+ receptor forms of EGFR with selectivity margin over wild-type EGFR. This study aims to explore the safety, tolerability, pharmacokinetic characteristics and efficacy of WSD0922-FU in patients with non-small cell lung cancer (NSCLC) with C797S mutation after first-line third-generation EGFR-TKI resistance.

Вмешательства

• Препарат WSD0922-FU
  Procedure: Biospecimen Collection - blood samples Undergo collection of blood samples Procedure: Computed Tomography and/or Magnetic Resonance Imaging Undergo CT and/or MRI Drug: WSD0922-FU Given PO

Первичные конечные точки

• ORR by IRC [Срок оценки: every 6 weeks, up to 1 year]
• PartA: To evaluate the safety of WSD0922-FU in patients with NSCLC [Срок оценки: 8 months]
• PartA: To evaluate the tolerability of WSD0922-FU in patients with NSCLC [Срок оценки: 8 months]
• PartA: To evaluate the Maximum Tolerated Dose (MTD) of WSD0922-FU in patients with NSCLC [Срок оценки: 8 months]
• PartA: Recommended Phase II Dose (RP2D) of WSD0922-FU in patients with NSCLC [Срок оценки: 8 months]

Вторичные конечные точки (12)

• PK exposure parameter: Maximum Plasma Concentration (Cmax) [Срок оценки: 12 months]
• PK exposure parameter: Time To Maximum Plasma Concentration (Tmax) [Срок оценки: 12 months]
• PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Time With Last Measurable Concentration (AUC0-t) [Срок оценки: 12 months]
• PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Infinity (AUC0-∞) [Срок оценки: 12 months]
• PK exposure parameter: Terminal Elimination Half-Life (t½) [Срок оценки: 12 months]
• PK exposure parameter: Apparent Terminal Elimination Rate Constant (λz) [Срок оценки: 12 months]
• PK exposure parameter: Apparent Clearance (CL) [Срок оценки: 12 months]
• PK exposure parameter: Apparent volume of distribution (Vd) [Срок оценки: 12 months]
• PK exposure parameter: Mean Residence Time (MRT) [Срок оценки: 12 months]
• Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve（AUCss） [Срок оценки: 12 months]
• Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve from 0 to Infinity（AUC0-∞,ss） [Срок оценки: 12 months]
• Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve from 0 to Time t （AUC0-t,ss） [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Age 18-75 years old (including the threshold value), gender is not limited;
• Locally advanced or metastatic NSCLC confirmed by pathology;
• Patients who have been genetically tested to carry EGFR sensitive mutations;
• Blood samples must be provided for testing and must be taken during or after disease progression following the last EGFR TKI inhibitor treatment;
• Must have a minimum life expectancy of >= 3 months;
• At least one measurable tumor lesion according to RECIST version 1.1; Previous radiotherapy-treated lesions cannot be used as target lesions unless imaging studies show clear progression of the lesions.
• Physical Status (ECOG PS) score was 0-1;
• Have full organ function;
• Eligible patients (male and female) who are fertile must agree to use a reliable contraceptive method ;
• Subjects are required to give informed consent to this study before the experiment and sign a written informed consent voluntarily.

Критерии исключения

• Received chemotherapy, radiotherapy, biological therapy, targeted therapy, endocrine therapy, immunotherapy, or other anti-tumor drug treatments within 4 weeks before the first administration of the study drug.
• Have previously received more than one EGFR-TKI inhibitor;
• Received other unlisted clinical study drugs or treatments within 4 weeks before the first administration.
• Received major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks before the first administration, or require elective surgery during the trial period.
• Used strong CYP3A4 inhibitors or strong CYP3A4 inducers within 7 days before the first use of the study drug.
• Known active brain metastasis or progression evidence.
• Other primary malignant tumors within 2 years before the first administration of the study drug.
• Adverse reactions from previous anti-tumor treatments have not recovered to NCI-CTCAE v5.0 grade ≤1 (except for toxicities judged by the researcher to have no safety risks, such as hair loss, grade 2 peripheral neurotoxicity, and stable thyroid function after hormone replacement therapy).
• Skin/pressure ulcers, chronic leg ulcers, known active gastric ulcers, or non-healing wounds.
• History of severe allergies, or allergies to any active or inactive ingredients of the study drug;
• Severe infections requiring intravenous antibiotic infusion or hospitalization at the time of screening; or uncontrollable active infections within 4 weeks before administration;
• Known active or suspected autoimmune diseases; or known active ocular diseases (such as active wet age-related macular degeneration, diabetic retinopathy with macular edema);
• Human immunodeficiency virus (HIV) (HIV1/2 antibody) positive, syphilis spirochete antibody positive .
• Patients with interstitial lung disease.
• History of severe cardiovascular diseases.
• Unable to orally swallow medication, or there is a condition that significantly affects gastrointestinal absorption as judged by the researcher;
• Clinical intervention is required for pleural effusion, ascites (excluding subjects who do not need drainage and have been stable for more than 2 weeks after drainage).
• Known alcohol or drug dependence.
• Mental disorders or poor compliance;
• Pregnant or lactating women;
• The investigator believes that the subject has other reasons that make them unsuitable for participating in this clinical study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 12 центров

• Anhui Provincial Hospital — Хэфэй
• Cancer Hospital Chinese Academy of Medical Sciences — Пекин
• The First Affiliated Hospital, Sun Yat-sen University — Гуанчжоу
• He'nan Cancer Hospital — Чжэнчжоу
• Shandong Cancer Hospital — Цзинань
• Shanghai Chest Hospital — Шанхай
• Shanghai East Hospital — Шанхай
• Shanghai Pulmonary Hospital — Шанхай
• … и ещё 4 центра

Идентификаторы

NCT: NCT06631989 · WSD0922-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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