A Study of XZB-0004 in Patients With Solid Tumors

Официальное название

A Phase I, Open-label, Dose-escalation Study of the Safety, Pharmacokinetics and Efficacy of the XZB-0004 in Patients With Solid Tumours

Обзор

XZB-0004 is a novel and potent small molecule inhibitor of receptor tyrosine kinase AXL. This is an open-label, multicentre phase I study of XZB-0004 in patients with solid tumors. Part 1 is a dose-escalation study to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic profile of XZB-0004, and then to identify a safe and pharmacologically active dose for evaluation in subsequent cohorts or clinical studies. Part 2 is a study to evaluate the efficacy and safety of XZB-0004 combined with Penpulimab in patients with NSCLC or advanced solid tumors.

Вмешательства

• Препарат XZB-0004
  Part 1a: 100mg BID, 150mg BID, and 200mg BID of XZB-0004 are planned to be evaluated, and the possibility of exploring higher or lower doses is not ruled out. Continuous administration of XZB-0004 for 21 days is a treatment cycle. Part 1b: XZB-0004 in combination with Penpulimab in subjects with advanced NSCLC or solid tumors, starting at a dose level down from the RP2D of XZB-0004 monotherapy- cohort 1: Advanced or metastatic NSCLC with advanced disease progression after treatment with PD-1 or

Первичные конечные точки

• Maximum tolerated dose (MTD) (for Part 1a) [Срок оценки: Up to 3 weeks]
• Recommended phase 2 dose (RP2D）(for Part 1a) [Срок оценки: Up to 3 weeks]
• Overall Response Rate (ORR) (for Part 1b) [Срок оценки: Up to 2-3 years]

Вторичные конечные точки (12)

• Pharmakinetic parameter - AUC0-t (for Part 1a and Part 1b) [Срок оценки: Up to 63 days]
• Pharmakinetic parameter - AUC0-∞ (for Part 1a and Part 1b) [Срок оценки: Up to 63 days]
• Pharmakinetic parameter - Cmax (for Part 1a and Part 1b) [Срок оценки: Up to 63 days]
• Pharmakinetic parameter - Tmax (for Part 1a and Part 1b) [Срок оценки: Up to 63 days]
• Pharmakinetic parameter - t½ (for Part 1a and Part 1b) [Срок оценки: Up to 63 days]
• Pharmakinetic parameter - CL/F (for Part 1a and Part 1b) [Срок оценки: Up to 63 days]
• Pharmakinetic parameter - Vz/F (for Part 1a and Part 1b) [Срок оценки: Up to 63 days]
• Overall Response Rate (ORR) (for Part 1a) [Срок оценки: Up to 2-3 years]
• Progression free survival (PFS) (for Part 1a and Part 1b) [Срок оценки: Up to 2-3 years]
• Duration of response (DOR) (for Part 1a and Part 1b) [Срок оценки: Up to 2-3 years]
• Disease control rate (DCR) (for Part 1a and Part 1b) [Срок оценки: Up to 2-3 years]
• Overall survival (OS) (for Part 1a and Part 1b) [Срок оценки: Up to 2-3 years]

Критерии участия

Критерии включения

• Patient has signed informed consent before any trial related activities.
• Be 18 years of age or older and less than 75 years at the time of signing the informed consent.
• Part 1: Have a histologically or cytologically confirmed diagnosis of a solid tumour malignancy; Part 2：Have a histologically or cytologically confirmed diagnosis of a NSCLC or solid tumour malignancy.
• Have evaluable (for Part 1) or measurable (for Part 2) disease as the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1.
• Have a performance status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.
• Have adequate organ function.
• Have recovered to ≤ grade 1 or Meet the requirements of the study from the effects of any prior cancer therapy, except for alopecia; irreversible neuropathy should have recovered to ≤ grade 2.
• Have a life expectancy greater than 3 months.
• Eligible patients (male and female) who are fertile must agree to at least use a reliable contraceptive method with partner.
• Willingness to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Критерии исключения

• Previous use of AXL inhibitors and immunotherapy was consistent with protocol requirements.
• Received anti-tumor therapy such as chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy or other therapy within 4 weeks prior to the first dose of the investigational drug.
• Received other unmarketed investigational drugs or treatments within 4 weeks or 5 times the elimination half-life prior to the first dose of the investigational drug.
• Treatment with systemic glucocorticoids (prednisone > 10mg per day or equivalent) or other immunosuppressive agents within 14 days before the first dose of a trial drug.
• Inability to swallow, intestinal obstruction or other factors that affect the taking and absorption of the drug.
• Patient with heart function impaired or clinically significant heart disease.
• Any condition or illness that, in the opinion of the Investigator, would interfere with the evaluation of the safety of the study drug.
• History of immune deficiencies, including positive HIV antibody tests.
• Patient is in the active stage of HBV or HCV.
• History of solid organ transplant or bone marrow transplant.
• Any other malignant tumor has been diagnosed within 5 years.
• Has known Primary tumor of the central nervous system or central nervous system metastase.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage were present within 4 weeks before the first dose of the trial drug.
• Subjects with psychiatric disorders that may affect trial compliance.
• history of Alcoholism or drug abuse.
• Pregnant or breastfeeding.
• The researchers considered that there were some cases that were not suitable for inclusion.

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

• Shanghai Pulmonary Hospital — Шанхай

Идентификаторы

NCT: NCT05772455 · XZB-0004-1001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗