A Study of the Oral EGFR Inhibitor PLB1004 in Non-Small Cell Lung Cancer

Официальное название

A Phase I Open-label, Multi-dose, Dose Escalation and Dose Expansion Study of the Oral EGFR Inhibitor PLB1004 in Non-Small Cell Lung Cancer

Обзор

This is a Phase I, multicenter, open-label, dose escalation and dose expansion study to assess the safety and pharmacokinetic profile of PLB1004, a mono-anilino-pyrimidine compound, given alone in NSCLC patients with EGFR exon 20 insertion mutations，uncommon mutations, classical mutations (Ex19del and L858R), and drug-resistant mutation (T790M). Patients will be enrolled and dosed according to the most current protocol. This study is made of two Parts. Part 1 includes a dose escalation into 7 cohorts and patient allocation to these cohorts will be via slot allocation. Each cohort has a minimum of 3 and a maximum of 6 patients for a total of 21 - 42 patients. The patient population of the dose escalation phase will include patients with advanced NSCLC harboring EGFR classical mutations or Ex20ins mutations, or uncommon mutations. Part 2 includes an expansion phase and the expansion phase will explore one or more dose levels of PLB1004 in NSCLC patients with EGFR Ex20ins mutations, classical mutations, or uncommon mutations.

Вмешательства

• Препарат PLB1004
  PLB1004 will be orally self-administered by the patient as a mono-therapy.

Первичные конечные точки

• Safety profile of PLB1004 per CTCAE v5.0 [Срок оценки: Up to 2 years]

Вторичные конечные точки (10)

• To define the DLTs and MTD [Срок оценки: Up to 3 years]
• Area Under the Curve (AUC) of PLB1004 [Срок оценки: Approximately 28 days.]
• Maximum plasma concentration (Cmax) of PLB1004 [Срок оценки: Approximately 28 days.]
• Time to maximum plasma concentration (Tmax) of PLB1004 [Срок оценки: Approximately 28 days.]
• Overall Response Rate (ORR) [Срок оценки: Up to 3 years]
• Progression-Free Survival (PFS) [Срок оценки: Up to 3 years]
• Overall Survival (OS) [Срок оценки: Up to 3 years]
• Disease Control Rate (DCR) [Срок оценки: Up to 3 years]
• Duration of Response (DOR) [Срок оценки: Up to 3 years]
• Change from baseline in corrected QT interval (QTc) using Fridericia formula (QTcF) [Срок оценки: Up to 3 years]

Критерии участия

Критерии включения

• Ability to understand and willingness to sign a written informed consent document;
• Male or female adult patients 18 years of age or older;
• Patients should have recovered from toxicities related to prior anti-tumor therapy;
• Patients should have recovered from the effects of major surgery;
• Have a documented EGFR mutation by a local test in tissue or plasma;
• At least 12 weeks life expectancy;
• Must have at least one measurable lesion per RECIST v 1.1;
• Sexually active males and females of childbearing potential must agree to take effective contraceptive measures.

Критерии исключения

• Received radiotherapy within 14 days before enrollment;
• Have significant or uncontrolled systemic disease;
• Have significant or uncontrolled cardiovascular disease;
• Have had other diagnosed malignant diseases that required treatment within the past 3 years besides NSCLC;
• Currently have or had a history of interstitial lung disease, drug-induced interstitial lung disease, or radiation pneumonia that requires steroid therapy;
• Have known hypersensitivity to the similar drugs and excipients of PLB1004;
• Pregnant or lactating women;
• Have used other experimental drugs within 2 weeks prior to the first dose of PLB1004;
• Have any condition or illness that could affect the compliance with the protocol.

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

США · 7 центров

• University of California-Davis — Sacramento
• Research Site — Louisville
• Nebraska Cancer Specialists — Omaha
• Research Site — New York
• Sarah Cannon Research Institute — Nashville
• Swedish Health Sciences — Seattle
• Research Site — Seattle

Идентификаторы

NCT: NCT06046495 · PLB1004-I-US01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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