AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia

Официальное название

A Phase 1/2 Study to Evaluate the Safety and Efficacy of AZD0486 in Adolescent and Adult Participants With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia

Обзор

This is a Phase 1/2, global multicentre, open-label, single-arm, dose escalation and dose optimisation study of AZD0486 to evaluate the safety, tolerability, and efficacy of AZD0486 monotherapy in participants with R/R B ALL who have received ≥ 2 prior lines of therapies. The study will consist of 3 parts. Part A monotherapy dose escalation. Part B dose optimisation. Part C Dose expansion at the recommended phase 2 dose (RP2D)

Подробное описание

This dose escalation and optimization study is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy in r/r B-ALL.

Вмешательства

• Препарат AZD0486
  Investigational Product administered via intravenous infusion.

Первичные конечные точки

• Part A: Frequency of DLTs [Срок оценки: Up to 28 days]
• Parts A & B: Safety Evaluation of AZD0486 [Срок оценки: From signing of informed consent through data cutoff, up to 42 months]
• Parts B & C: Rate of CR within 3 cycles [Срок оценки: Up to three cycles of 28 days each]

Вторичные конечные точки (12)

• Part A: Rate of CR within 3 cycles [Срок оценки: Up to 3 cycles of 28 days each]
• Part A,B,C: Rate of CR/CRh and CR/CRh/CRi within 3 cycles [Срок оценки: Up to 3 cycles of 28 days each]
• Parts A, B, C: Rate of CR, CR/CRh and CR/CRh/CRi at any time during the study [Срок оценки: From first dose to end of treatment or data cutoff, whichever comes first, assessed up to 42 months]
• Parts A, B, C: Duration of CR, CR/CRh and CR/CRh/CRi [Срок оценки: From first dose to last progression or data cutoff, whichever comes first, assessed up to 42 months]
• Parts A, B, C: Event-free survival (EFS) [Срок оценки: From First dose to last progression or data cutoff, whichever comes first, assessed up to 42 months]
• Parts A, B, C: Overall Survival (OS) [Срок оценки: From First dose to data cutoff, up to 42 months]
• Parts B &C: Subsequent alloSCT or donor lymphocyte infusion if used as an alloSCT substitute [Срок оценки: From first dose to EOT, up to 42 Months]
• Part A, B, C:MRD-negative rate of CR [Срок оценки: From First dose to data cutoff, up to 42 months]
• Parts A, B, & C: PK characterization of AZD0486 [Срок оценки: From first dose to data cutoff, up to 42 months]
• Parts A, B & C: PK Characterization of AZD0486 [Срок оценки: From first dose to data cutoff, up to 42 months]
• Parts A, B, C: PK Characterization of AZD0486 [Срок оценки: From first dose to data cutoff, up to 42 months]
• Parts A, B, C: PK Characterization of AZD0486 [Срок оценки: From first dose to data cutoff, up to 42 months]

Критерии участия

Критерии включения

• Age: 12 years and above (Parts A, B and C).
• Participants with B-cell Acute Lymphoblastic Leukemia with CD19 expression by local lab with:

• Bone marrow infiltration with >/= 5% blasts
• Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option.
• Philadelphia positive participants are allowed in all parts of the study, if intolerant or refractory to TKIs.
• For participants older than 16 years, Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2. For Participants 16 years or younger, Lansky score more or equal to 50%.

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

Критерии исключения

• Active CNS involvement by B-ALL, defined by presence of ALL blasts in CSF (CNS2 and CNS3 criteria).
• Isolated extramedullary disease relapse.
• Testicular leukemia
• History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; or prior Grade 4 neurotoxicity with CAR-T or TCE therapy.
• History of other malignancy (with certain exceptions).
• Unresolved AEs >/= Grade 2, from prior therapies
• Prior therapy with TCEs within 4 weeks, CAR T-cell therapy or autologous HSCT within 8 weeks or prior alloSCT within 12 weeks of start of therapy.
• GVHD requiring immunosuppressive therapy within 3 weeks prior to AZD0486 treatment.

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

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 12 центров

• Research Site — Birmingham
• Research Site — Duarte
• Research Site — Los Angeles
• Research Site — Palo Alto
• Research Site — Tampa
• Research Site — Atlanta
• Research Site — Chicago
• Research Site — New York
• … и ещё 4 центра

Германия · 11 центров

• Research Site — Cologne
• Research Site — Düsseldorf
• Research Site — Essen
• Research Site — Frankfurt
• Research Site — Freiburg im Breisgau
• Research Site — Halle
• Research Site — Hamburg
• Research Site — Kiel
• … и ещё 3 центра

Япония · 11 центров

• Research Site — Bunkyō City
• Research Site — Chiba
• Research Site — Chūōku
• Research Site — Fukuoka
• Research Site — Kashiwa
• Research Site — Kyoto
• Research Site — Okayama
• Research Site — Osaka
• … и ещё 3 центра

Китай · 10 центров

• Research Site — Чанша
• Research Site — Чэнду
• Research Site — Гуанчжоу
• Research Site — Гуанчжоу
• Research Site — Ханчжоу
• Research Site — Нанкин
• Research Site — Нанкин
• Research Site — Сучжоу
• … и ещё 2 центра

Франция · 6 центров

• Research Site — Caen
• Research Site — Marseille
• Research Site — Nantes
• Research Site — Paris
• Research Site — Pierre-Bénite
• Research Site — Toulouse

Испания · 6 центров

• Research Site — Barcelona
• Research Site — Barcelona
• Research Site — Madrid
• Research Site — Madrid
• Research Site — Salamanca
• Research Site — Valencia

Италия · 5 центров

• Research Site — Bergamo
• Research Site — Bologna
• Research Site — Monza
• Research Site — Naples
• Research Site — Roma

Тайвань · 5 центров

• Research Site — Kaohsiung City
• Research Site — Taichung
• Research Site — Tainan
• Research Site — Taipei
• Research Site — Taoyuan

South Korea · 4 центра

• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul

Бразилия · 3 центра

• Research Site — Porto Alegre
• Research Site — São Paulo
• Research Site — São Paulo

Канада · 3 центра

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

Великобритания · 3 центра

• Research Site — London
• Research Site — Manchester
• Research Site — Surrey

Австралия · 1 центр

• Research Site — Melbourne

Публикации

• Davis KL, Yao CC, Zimmerman JAO, Rau RE. Immunotherapy in B-Cell Acute Lymphoblastic Leukemia. J Natl Compr Canc Netw. 2025 Dec;23(12):e257067. doi: 10.6004/jnccn.2025.7067. PMID 41671463

Идентификаторы

NCT: NCT06137118 · D7405C00001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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