AZD0305 as Monotherapy or in Combination With Anticancer Agents in Participants With Multiple Myeloma

Официальное название

A Modular Phase I/II, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, Pharmacodynamics, and Preliminary Efficacy of AZD0305 as Monotherapy or in Combination With Anticancer Agent(s) in Participants With Multiple Myeloma

Обзор

This is a Phase I/II, modular, open-label, multicenter, dose escalation, and dose expansion/optimization study to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics and efficacy of AZD0305 as monotherapy and in combination with other anticancer agents in participants with MM.

Подробное описание

This study will follow a modular protocol design evaluating AZD0305 as monotherapy and in combination with other anticancer agents. The protocol may be amended in the future to incorporate further monotherapy expansion at the recommended Phase 2 dose (RP2D) in Phase II, and/or additional modules investigating AZD0305 in combination with other anticancer agents.

The study consists of 3 modules:

* Module 1 (AZD0305 monotherapy), * Module 2 (AZD0305 in combination with elranatamab) * Module 3 (AZD0305 in combination with pomalidomide and dexamethasone \[Pd\])

Вмешательства

• Препарат AZD0305
  AZD0305 Investigational product
• Препарат Elranatamab
  Module 2 Investigational product
• Препарат Pomalidomide
  Module 3 Standard of Care (background treatment)
• Препарат Dexamethasone
  Module 3 Standard of Care (background treatment)

Первичные конечные точки

• Occurrence of dose-limiting toxicity (DLT), as defined in the protocol (Phase Ia dose escalation only) [Срок оценки: From first dose of AZD0305 until the end of Cycle 1. Cycle 1 (the DLT assessment period is 21 days for Module 1 Group A and 28 days for Module 1 Group B, Module 2, and Module 3)]
• Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: From time of Informed consent to 30 days post end of treatment]
• Frequency of dose modifications, dose delays, and treatment discontinuations due to AEs (Module 2 and Module 3) [Срок оценки: From first dose of study treatment until End of treatment (EOT), assessed up to approximately 2 years (each cycle is 28 days)]

Вторичные конечные точки (12)

• Phase Ia: Objective Response Rate (ORR) [Срок оценки: From first dose of AZD0305 to progressive disease or Initiation of subsequent MM therapy (approximately 2 years)]
• Phase Ia: Duration of response (DoR) [Срок оценки: From the first documented response to confirmed progressive disease or death (approximately 2 years)]
• Phase Ia: Progression free Survival (PFS) [Срок оценки: From first dose of AZD0305 to progressive disease or death in the absence of disease progression (approximately 2 years)]
• Phase Ia: Overall Survival (OS) [Срок оценки: From first dose of AZD0305 to death (approximately 2 years)]
• Phase Ia: Pharmacokinetics of AZD0305: Area Under the concentration-time curve (AUC) [Срок оценки: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Pharmacokinetics of AZD0305: Maximum plasma concentration of the study drug (Cmax) [Срок оценки: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Pharmacokinetics of AZD0305: Time to maximum plasma concentration of the study drug (tmax) [Срок оценки: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Pharmacokinetics of AZD0305: Clearance [Срок оценки: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Pharmacokinetics of AZD0305: Terminal elimination half-life (t 1/2) [Срок оценки: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Immunogenicity of AZD0305 [Срок оценки: From the first dose of study intervention, at predefined intervals throughout the administration of AZD0305 (approximately 2 years)]
• Phase Ia: Immunogenicity of elranatamab [Срок оценки: From the first dose, at predefined intervals until Cycle 24 administration of elranatamab(approximately 2 years)]
• Phase Ia: MRD negative CR rate [Срок оценки: From first dose of AZD0305 to progressive disease or death in the absence of disease progression (approximately 2 years)]

Критерии участия

Критерии включения

• Participants must be at least 18 years of age or the legal age of consent in the jurisdiction
• in which the study is taking place;
• Eastern Cooperative Oncology Group performance status of ≤ 2 in module 1, or 0 or 1 in modules 2 and 3;
• Documentation of Multiple Myeloma (MM) as defined by International Myeloma Working Group (IMWG) Diagnostic Criteria for Multiple Myeloma. Site should ensure that Multiple Myeloma diagnosis is confirmed in accordance with the IMWG Diagnostic Criteria;
• Participants must have one or more measurable disease criteria for Serum M-Protein, Urine M-protein, and Serum immunoglobulin free light chains as specified in the relevant module of the CSP;
• Adequate organ and bone marrow function assessment at screening according to the hematological, hepatic, and renal parameters listed in the CSP as relevant to each module;
• Participants must have received at least 3 prior lines of treatment in module 1, or 1-3 prior lines in modules 2 and 3, with additional module-specific requirements related to prior lines of therapy

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

Критерии исключения

• Amyloidosis, plasma cell leukemia, Waldenstrom Macroglobulinemia, Polyneuropathy Organomegaly Endocrinopathy M-protein and Skin Syndrome, or Smoldering Multiple Myeloma (compliant with WHO criteria);
• Participants exhibiting clinical signs of central nervous system involvement of MM;
• Participants with known COPD, or previous history of ILD/pneumonitis;
• Participants with known moderate or severe persistent asthma within the past 5 years, or uncontrolled asthma of any classification;
• Participants who have severe cardiovascular disease which is not adequately controlled;
• Participants who have a history of immunodeficiency disease;
• Participants with peripheral neuropathy ≥ Grade 2;
• Primary refractory MM;
• Participants who have previously received anti-GPRC5D or MMAE-containing treatment;
• Participants who have previously received allogenic stem cell transplant, or participant has received autologous stem cell transplant within 3 months before the first dose of study intervention;
• Participants with a history of prior malignancy other than MM within 3 years prior to first dose of study intervention. some exceptions apply;
• Participants with previous history of active JC virus infection resulting in PML;
• Participants with a known hypersensitivity to AZD0305 or any of the excipients of the product or to any of the drugs included in the respective modules or who experienced Grade 3 or higher hypersensitivity to prior monoclonal antibody therapy;
• Participants who have uncontrolled severe illness including but not limited to ongoing active infection requiring therapeutic antibiotics and/or other administration

The above is a summary of key criteria, 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 · 9 центров

• Research Site — Duarte
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Германия · 8 центров

• Research Site — Essen
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Канада · 5 центров

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Испания · 5 центров

• Research Site — Badalona
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Австралия · 4 центра

• Research Site — Fitzroy
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Китай · 4 центра

• Research Site — Пекин
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Бразилия · 3 центра

• Research Site — Salvador
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• Research Site — São Paulo

Япония · 3 центра

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Франция · 2 центра

• Research Site — Lille
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Идентификаторы

NCT: NCT06106945 · D7230C00001 · 2023-508590-89-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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