A Phase I, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Cellular Kinetics, Immunogenicity, Pharmacodynamics, and Preliminary Efficacy of AZD0120 in Participants With Multiple Myeloma (DURGA-2)

Официальное название

A Modular, Phase I, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Cellular Kinetics, Immunogenicity, Pharmacodynamics, and Preliminary Efficacy of AZD0120, a Dual-targeting Autologous Chimeric Antigen Receptor T-cell (CAR-T) Therapy Directed Against BCMA and CD19 in Participants With Multiple Myeloma (DURGA-2)

Обзор

This is an interventional, modular, open-label, multicenter study to primarily evaluate the safety and tolerability of AZD0120 in adult participants with multiple myeloma (MM).

Подробное описание

This modular study aims to evaluate the safety, tolerability, cellular kinetics, pharmacodynamic effect, immunogenicity, and preliminary efficacy of AZD0120 in subjects with newly diagnosed or early relapsed or primary refractory multiple myeloma. Module 1 consists of early line MM (including newly diagnosed MM and early relapsed or primary refractory MM) with AZD0120 (for newly diagnosed multiple myeloma (NDMM), the intervention is with AZD0120 ± maintenance). Module 2 consists of NDMM with AZD0120 ± maintenance.

Вмешательства

• Биопрепарат AZD0120
  AZD0120 is a BCMA/CD19 dual CAR T cell product under investigation for early-line treatment in subjects with multiple myeloma

Первичные конечные точки

• Adverse Events (AEs) [Срок оценки: 2 years]
• Serious Adverse Events (SAEs) [Срок оценки: 2 years]
• Dose Limiting Toxicities (DLT) [Срок оценки: 28 days]

Вторичные конечные точки (12)

• Pharmacokinetic - AUC0-28d [Срок оценки: 0-28 Days]
• Pharmacokinetic AUC0-3M [Срок оценки: 0 - 3 Months]
• Pharmacokinetic AUClast [Срок оценки: 2 years]
• Pharmacokinetic - Cmax [Срок оценки: 2 years]
• Pharmacokinetic - Tmax [Срок оценки: 2 years]
• Pharmacokinetic - Clast [Срок оценки: 2 years]
• Pharmacokinetic - Tlast [Срок оценки: 2 years]
• Pharmacokinetic - Quantification of CAR transgene levels [Срок оценки: 2 years]
• Efficacy - Objective Response Rate (ORR) [Срок оценки: 2 years]
• Efficacy - Complete Response Rate (CRR) [Срок оценки: 2 years]
• Efficacy - Minimal Residual Disease (MRD) Negative CR Rate at 9 Months (± 3 months) [Срок оценки: 9 months]
• Efficacy - Sustained Minimal Residual Disease (MRD) Negative CR Rate [Срок оценки: 2 years]

Критерии участия

Критерии включения

Age:

• Males and females ≥18 years of age at the time of consent

Type of Participant and Disease Characteristics:

• Participant must have documented diagnosis of MM per IMWG diagnostic criteria
• ECOG performance status of 0 or 1.
• Adequate organ and bone marrow function.

For NDMM participants:

• Participants on Module 1: Newly diagnosed multiple myeloma (NDMM) without prior anti- myeloma therapy (no more than 2 cycles of induction therapy before enrollment are acceptable)
• For participants on Module 2: Newly diagnosed MM with a minimum of 4 cycles and a maximum of 6 cycles of induction therapy completed prior to screening
• Classified as high-risk MM

For Early Relapsed or Primary Refractory MM (1 or 2 prior lines of therapy) participants:

• Have received and failed 1 or 2 lines of anti-myeloma therapy
• Have received a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) as part of their previous therapy
• Have documented evidence of progressive disease based on investigator's determination of response by the IMWG criteria within 1 year of starting treatment, or on or within 6 months of completing treatment of the subject's last line of anti-myeloma therapy, or have confirmed progressive disease within 6 months prior to screening and who are subsequently determined to be refractory or non-responsive to their most recent anti-myeloma treatment regimen

General Exclusion Criteria:

• Have received prior treatment with CAR T therapy directed at any target
• Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma
• Active or history of plasma cell leukemia at the time of screening
• Seropositive for human immunodeficiency virus (HIV)
• Active Hepatitis B infection
• Active Hepatitis C infection
• Serious underlying medical condition

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

США · 13 центров

• Research Site — Phoenix
• Research Site — Duarte
• Research Site — Denver
• Research Site — Tampa
• Research Site — Atlanta
• Research Site — Iowa City
• Research Site — Rochester
• Research Site — St Louis
• … и ещё 5 центров

Идентификаторы

NCT: NCT07073547 · D831EC00001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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