A Study to Evaluate Safety, PK, PD and Efficacy of AZD5492, a T Cell-engaging Antibody Targeting CD20 in Subjects With R/R B-Cell Malignancies.

Официальное название

A Modular Phase I/II Open-label Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD5492, a T Cell-engaging Antibody Targeting CD20 in Subjects With Relapsed or Refractory B-Cell Malignancies (TITANium)

Обзор

This is a Phase I/II study designed to evaluate if experimental T cell engaging antibody targeting CD20 AZD5492 is safe, tolerable and efficacious in participants with Relapsed or Refractory B-Cell Malignancies.

Вмешательства

• Препарат AZD5492
  CD8/TCR based T-cell engaging antibody targeting CD20, which is administered subcutaneously

Первичные конечные точки

• Frequency of dose limiting toxicities (DLTs). [Срок оценки: Module 1 - From the first administration of AZD5492 until the end of cycle 1 (up to 5 weeks).]
• Safety evaluation of AZD5492: Number of participants with treatment-related adverse events. [Срок оценки: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.]
• Tolerability evaluation of AZD5492: Number of participants with treatment-related adverse events. [Срок оценки: Module 1 - From the first administration of AZD5492 within the duration of the treatment period, up to and including 90 (+7) days after the last dose of study treatment , but prior to subsequent cancer therapy.]

Вторичные конечные точки (12)

• Overall Response Rate (ORR) [Срок оценки: Module 1 - From first dose of AZD5492 up to 2 years after last dose.]
• Complete Response Rate (CR Rate) [Срок оценки: Module 1 - From first dose of AZD5492 up to 2 years after last dose.]
• Duration of Response (DoR) [Срок оценки: Module 1 - From first dose of AZD5492 up to 2 years after last dose.]
• Progression-free Survival (PFS) [Срок оценки: Module 1 - From first dose of AZD5492 up to 2 years after last dose.]
• Overall Survival (OS) [Срок оценки: Module 1 - From first dose of AZD5492 up to 2 years after last dose.]
• Pharmacokinetics of AZD5492: serum concentration of study drug [Срок оценки: Module 1 - From informed consent until 90 days after last dose of AZD5492.]
• Pharmacokinetics of AZD5492: Maximum plasma concentration of the study drug (Cmax). [Срок оценки: Module 1 - From informed consent until 90 days after last dose of AZD5492.]
• Pharmacokinetics of AZD5492: Area under the concentration time curve (AUC). [Срок оценки: Module 1 - From informed consent until 90 days after last dose of AZD5492.]
• Pharmacokinetics of AZD5492: apparent clearance [Срок оценки: Module 1 - From informed consent until 90 days after last dose of AZD5492.]
• Pharmacokinetics of AZD5492: Half-life (t 1/2) [Срок оценки: Module 1 - From informed consent until 90 days after last dose of AZD5492.]
• To determine the immunogenicity of AZD5492 [Срок оценки: Module 1 - From informed consent until 90 days after last dose of AZD5492.]
• To determine the immunogenicity of AZD5492 [Срок оценки: Module 1 - From informed consent until 90 days after last dose of AZD5492.]

Критерии участия

Критерии включения

• ≥18 years of age;
• Histologically documented CD20+ mature B-cell neoplasm

• Large B-cell lymphoma
• Follicular lymphoma
• Mantle cell lymphoma
• Chronic lymphocytic leukemia
• Small lymphocytic lymphoma
• Relapsed, progressive and/or refractory disease following at least 2 prior lines of therapy;
• ECOG performance status of ≤ 2 (< 2 in EU countries).

The above is a summary, other inclusion criteria details may apply.

Критерии исключения

• Any neoplasm histology not specified in the IC section;
• Active CNS involvement in lymphoma;
• CNS pathology including but not limited to any history of seizure disorder/epilepsy;
• Prior allogeneic HSCT within 180 days, prior autologous HSCT within 90 days, or cell therapy within 90 days of start of therapy;
• History of Grade ≥ 3 CRS or Grade ≥ 3 ICANS;
• Active and uncontrolled infections;
• Unresolved AEs ≥2 Grade due to prior anticancer therapies, with some exceptions

The above is a summary, other exclusion criteria details may apply.

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 · 10 центров

• Research Site — La Jolla
• Research Site — Boston
• Research Site — Rochester
• Research Site — Hackensack
• Research Site — New York
• Research Site — New York
• Research Site — Charlotte
• Research Site — Winston-Salem
• … и ещё 2 центра

Германия · 4 центра

• Research Site — Göttingen
• Research Site — München
• Research Site — Ulm
• Research Site — Würzburg

Канада · 3 центра

• Research Site — Calgary
• Research Site — Toronto
• Research Site — Montreal

Испания · 3 центра

• Research Site — Barcelona
• Research Site — L'Hospitalet de Llobregat
• Research Site — Madrid

Австралия · 2 центра

• Research Site — Melbourne
• Research Site — Nedlands

Китай · 2 центра

• Research Site — Ханчжоу
• Research Site — Шанхай

Франция · 2 центра

• Research Site — Pessac
• Research Site — Villejuif

Италия · 2 центра

• Research Site — Bologna
• Research Site — Milan

Япония · 2 центра

• Research Site — Chūōku
• Research Site — Kashiwa

Дания · 1 центр

• Research Site — København Ø

Идентификаторы

NCT: NCT06542250 · D9960C00001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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