Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ICP-248 as Monotherapy or in Combination With Anti-CD20 Monoclonal Antibody in Mature B-cell Malignancies

Официальное название

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ICP-248 as Monotherapy or in Combination With Anti-CD20 Monoclonal Antibody in Patients With Mature B-cell Malignancies

Обзор

Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ICP-248 as monotherapy or in combination with anti-CD20 monoclonal antibody in Mature B-cell Malignancies

Вмешательства

• Препарат ICP-248
  ICP-248 will be administered orally once daily at escalated doses (starting dose 5/10 mg, maximum 150 mg).
• Препарат Obinutuzumab (G)
  Obinutuzumab will be administered by IV infusion at a dose of 100 mg or 1000 mg, depending on splitting rules, at Cycle 1, Day 1 (if 100 mg was received on Day 1, 900 mg will be administered on Cycle 1, Day 2); 1000 mg at Cycle 1, Day 8 and Day 15; 1000 mg at Day 1 for all subsequent cycles until the end of Cycle 6.
• Препарат Rituximab (R)
  Rituximab will be administered by IV infusion at a dose of 375 milligrams per square meter (mg/m\^2) at Day 1 per week for 4 weeks during cycle 1, then on day 1 of cycles 3-8, and thereafter once every other cycle up to 2 years.

Первичные конечные точки

• DLT [Срок оценки: 49 days]
• Safety and tolerability of ICP-248 at different doses in B-cell malignancies [Срок оценки: 5 years]

Вторичные конечные точки (3)

• Cmax, ss of ICP-248 [Срок оценки: Predose up to week 28]
• Ctrough, ss of ICP-248 [Срок оценки: Predose up to week 28]
• Preliminary efficacy of ICP-248 monotherapy in patients with B-cell malignancy [Срок оценки: 5 years]

Критерии участия

• Age ≥ 18.
• Subjects with histopathologically and/or flow cytometry-confirmed diseases according to the 2016 World Health Organization (WHO) classification criteria for lymphohematopoietic neoplasms or meeting the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria: relapsed or refractory CLL/SLL, relapsed or refractory MCL. Patients must have received at least two prior lines of adequate systemic therapy before study entry, and at least one prior systemic therapy should include Bruton's kinase inhibitor (BTKi).
• For subjects with R/R MCL: Patients must have measurable disease per the Lugano 2014 criteria.
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of ≤ 1 and a life expectancy of ≥ 6 months.
• Adequate hematologic, hepatic, renal, pulmonary and cardiac function
• Patients with basically normal coagulation function
• Patients with fertility potential and their partners need contraception
• Subjects can communicate with the investigator well and to complete the study as specified in the study.

Критерии исключения

• Known central nervous system involvement by lymphoma/leukemia.
• Known or suspected history of Richter's transformation.
• Prior autologous stem cell transplant (unless ≥ 3 months since transplant); or prior chimeric cell therapy (unless ≥ 3 months since cell infusion).
• A history of allogeneic stem cell transplantation.
• An interval of less than 5 half-lives from the last dose of a strong CYP3A or CYP2C8 inhibitor or inducer (chemical agent, herbal medicine and dietary supplement) to the first dose of the investigational product, or a plan to use concurrently medications, dietary supplements or food (e.g., grapefruit or grapefruit juice) with strong CYP3A or CYP2C8 inhibitory or inductive effect during study participation
• Presence of active infection that currently requires intravenous systemic anti-infective therapy.
• History of immunodeficiency, including a positive human immunodeficiency virus (HIV) antibody test.
• History of significant cardiovascular disease
• Patients with previous or concomitant central nervous system disorders
• Grade 2 or above toxicity due to prior anti-cancer therapy at screening
• Known alcohol or drug dependence
• Unable to swallow tablets or presence of disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Украина · 5 центров

• CNE CCOHTPC of Cherkasy Regional Council — Cherkasy
• CNE"City Clin Hosp#4"of Dnipro City Council — Dnipro
• Medical Center of Limited Liability Company Arensia Exploratory Medicine — Kyiv
• Med Center 'Ok!Clinic+' of International Institute of Clinical Trials LLC — Kyiv
• SI Institute of Blood Pathology and Transfusion Medicine of AMSU — Lviv

США · 2 центра

• BRCR Medical Center — Plantation
• Clinical Research Alliance — Westbury

Пуэрто-Рико · 1 центр

• Pan American Center for Oncology Trials — San Juan

Идентификаторы

NCT: NCT06351527 · ICP-CL-01202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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