A Study of AZD2962, an IRAK4 Inhibitor (IRAK4 [a Body Protein] Blocker), in Participants With Haematologic Neoplasms (Blood Cancers)

Official title

A Modular Phase I/II, Open-label, Multicentre Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of AZD2962, an IRAK4 Inhibitor, as Monotherapy and in Combination With Other Agents, in Participants With Haematologic Neoplasms

Overview

The purpose of the study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of AZD2962, an Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) inhibitor, as monotherapy and in combination with other agents in participants with haematologic neoplasms.

Detailed description

This is a modular study. In Module 1, the study will begin with a dose escalation of AZD2962 monotherapy in participants with myelodysplastic syndromes (MDS) and dysplastic chronic myelomonocytic leukemia (CMML).

Module 1 of the study will comprise of:

1. A Screening Period of maximum 21 days. 2. Treatment period with 28-day cycles where each patient will receive an oral dose of AZD2962 once daily, starting on Day 1, and will continue treatment until disease progression, unacceptable toxicity, or withdrawal. 3. Safety Follow-up period after 30 days after last dose.

Interventions

• Drug AZD2962
  AZD2962 will be administered orally once daily.

Primary outcome measures

• Number of participants with dose limiting toxicity (DLT) [Time frame: From Cycle 1 Day 1 up to end of Cycle 1 (28 Days)]
• Number of participants with Adverse events (AEs) and serious AEs [Time frame: Cycle 1 Day 1 up to safety follow-up (30 days after last dose) (Approximately 3 years)]
• Duration of exposure [Time frame: Cycle 1 Day 1 up to safety follow-up (30 days after last dose) (Approximately 3 years)]
• Relative dose intensity [Time frame: Cycle 1 Day 1 up to safety follow-up (30 days after last dose) (Approximately 3 years)]

Secondary outcome measures (9)

• Percentage of participants with Objective response (OR) [Time frame: First dose up to progression of disease (PD) or last evaluable assessment in the absence of progression, whichever comes first (Approximately 3 Years)]
• Duration of response (DoR) [Time frame: First documented response, up to the date of the first documented PD or study end, which ever comes first (Approximately 3 Years)]
• Time to Response (TTR) [Time frame: First dose up to PD or last evaluable assessment, whichever comes first (Approximately 3 Years)]
• Overall Survival (OS) [Time frame: First dose up to death due to any cause (Approximately 3 Years)]
• Time to Progression to Acute myeloid leukaemia (AML) [Time frame: First dose up to first diagnosis of AML (Approximately 3 Years)]
• Plasma concentration of AZD2962 [Time frame: Cycle 1 Day 1 (each cycle is 28 days) up to end of the treatment (EoT) (Approximately 3 Years)]
• Area under the concentration time curve (AUC). [Time frame: Cycle 1 Day 1 (each cycle is 28 days) up to EoT (Approximately 3 Years)]
• Maximum plasma drug concentration (Cmax) [Time frame: Cycle 1 Day 1 (each cycle is 28 days) up to EoT (Approximately 3 Years)]
• Time to reach maximum concentration (tmax) [Time frame: Cycle 1 Day 1 (each cycle is 28 days) up to EoT (Approximately 3 Years)]

Eligibility criteria

Inclusion criteria

• Participants with relapsed/refractory MDS or participants with relapsed/refractory dysplastic CMML, with peripheral blasts or bone marrow blasts < 20%, and who received one or more prior lines of therapy as per standard of care (or who exhausted locally available treatments including treatments for actionable mutations). Diagnosis must be histologically confirmed as per the WHO 2016 classification of myeloid neoplasms.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Participants must have symptomatic disease that requires therapy and allows for objective efficacy assessments.
• Willing to provide baseline bone marrow aspirate (or biopsy if dry-tap).
• Contraceptive use by participants or participant partners should be consistent with local regulations and also comply with Clinical Study Protocol requirements.
• All women of childbearing potential must have a negative serum pregnancy test result at Screening.

Exclusion criteria

• Prior treatment with IRAK inhibitors or inhibitors of the inflammasome pathway.
• Received any antineoplastic therapy (except hydroxyurea) within 15 days prior to first dose.
• Received any strong or moderate Cytochrome P450 3A (CYP3A) inhibitors within 15 days prior to first dose.
• Received major surgery within 28 days prior to first dose, or still recovering from surgery.
• Received drugs that are known to prolong corrected QT interval (QTc) and with known risk of Torsades de Pointes, within 15 days prior to first dose.
• Received immunosuppressive medications (including Graft-Versus-Host Disease prophylaxis) within 28 days prior to first dose, or within 15 days in the case of systemic steroids (doses exceeding 10 mg/day of prednisone or equivalent).
• Received live attenuated vaccines within 28 days prior to first dose.
• Active major bleeding event.
• Any evidence of systemic disease, significant clinical disorder, or laboratory finding that make undesirable the participation in the study.

15\. Mean resting corrected QT interval using Fridericia's formula (QTcF) > 450 ms obtained from triplicate Electrocardiograms (ECGs) and averaged, recorded within 5 minutes. In the presence of bundle branch block, QTcF > 470 ms is applicable.

16\. History of intracranial bleeding within 6 months prior to first dose. 17. Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism or excretion of oral therapy.

18\. History of a prior non-haematologic neoplasm (with some exceptions). 19. Unresolved Grade > 2 toxicities from prior anticancer therapies (with some exceptions).

20\. Concurrent enrolment in another clinical study (with some exceptions). 21. Known hypersensitivity to study intervention or its excipients.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Spain · 6 centers

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

United States · 3 centers

• Research Site — Miami
• Research Site — Tampa
• Research Site — Houston

Taiwan · 3 centers

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

United Kingdom · 3 centers

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

Australia · 2 centers

• Research Site — Heidelberg
• Research Site — Melbourne

Japan · 2 centers

• Research Site — Shinagawa-ku
• Research Site — Yoshida-gun

South Korea · 2 centers

• Research Site — Seoul
• Research Site — Seoul

Identifiers

NCT: NCT07064122 · D7770C00001 · 2025-520786-44 · 172349

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗