A study of AZD2962, an IRAK4 inhibitor, in Participants with Haematologic Neoplasms

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

21 Oct 2025 → ongoing

Decision date (initial)

2025-08-11

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacogenomic, Pharmacokinetic, Others, Therapy, Pharmacodynamic

- To assess the safety and tolerability of AZD2962.
- To identify the Optimal Biological Dose.

Secondary objectives 2

1. To estimate the efficacy of AZD2962.
2. To characterise the PK of AZD2962 as monotherapy

Conditions and MedDRA coding

Myelodysplastic syndromes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participant must be at least 18 (or older as per the legal age of consent in the applicable jurisdiction) at the time of signing the informed consent.
2. Patients with R/R MDS or patients with R/R 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). Note: Participants with dysplastic CMML are only eligible for dose escalation cohort.
3. ECOG performance status of ≤ 2.
4. Patients must have symptomatic disease that requires therapy and allows for objective efficacy assessments.
5. Willing to provide baseline BMA (or biopsy if dry-tap).
6. Must meet the following laboratory parameters: a. WBC count ≤ 10.0 x 109/L (MDS patients), or < 13.0 x 109/L (CMML patients). Note: For MDS patients, treatment with hydroxyurea is permitted to lower the WBC to reach this inclusion criterion. The WBC should be determined ≥ 24 hours after the last dose of hydroxyurea; b. ALT and AST ≤ 3 × ULN; c. Serum TBL ≤ 1.5× ULN (≤ 3 × ULN in case of documented Gilbert’s Syndrome); d. Creatinine clearance ≥ 60 mL/min calculated by Cockcroft and Gault method.

Exclusion criteria 22

1. Prior treatment with IRAK inhibitors or inhibitors of the inflammasome pathway.
2. Received any antineoplastic therapy (except hydroxyurea) within 15 days prior to C1D1
3. Received major surgery (as defined by the investigator) within 28 days prior to C1D1, or still recovering from surgery.
4. Received drugs that are known to prolong QT and with known risk of Torsades de Pointes, within 15 days (or 5 half-lives, whichever is longer) prior to C1D1.
5. Received immunosuppressive medications (including GVHD prophylaxis) within 28 days prior to C1D1, or within 15 days in the case of systemic steroids (doses exceeding 10 mg/day of prednisone or equivalent).
6. Received live attenuated vaccines within 28 days prior to C1D1.
7. Active major bleeding event.
8. Any evidence of systemic disease (severe or uncontrolled), significant clinical disorder, or laboratory finding, that make undesirable the participation in the study.
9. Symptomatic heart failure (New York Heart Association Grade 2 to Grade 4), or hospitalisation for heart failure within 6 months prior to C1D1.
10. Acute coronary syndrome/myocardial infarction or percutaneous coronary intervention or coronary artery bypass graft within 6 months prior to C1D1.
11. Any planned revascularisation intervention or severe valvular heart disease.
12. Stroke or transient ischaemic attack within 6 months prior to C1D1.
13. LVEF < 50%.
14. Symptomatic and uncontrolled hypertension.
15. Mean resting QTcF > 450 ms obtained from triplicate 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 C1D1
17. Serologic status reflecting active hepatitis B or C infection: a. Participants with positive HBsAg will be excluded; b. Participants with anti-HBc IgG Ab positive will be excluded unless they have a negative HBV PCR result before enrolment (in this case HBV PCR will be monitored repeatedly while on study per institutional guidance); c. Participants with positive anti-HCV Ab will be excluded unless they have a negative HCV PCR result before enrolment.
18. Active HIV infection. Participants on an effective anti-retroviral therapy and sustained viral load undetectable for at least 6 months prior to enrolment, are eligible after confirmation from the Sponsor. HIV viral load must be monitored while on study per institutional guidance.
19. Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism or excretion of oral therapy (eg, ulcerative disease, uncontrolled nausea, vomiting, diarrhoea Grade ≥ 2, and malabsorption).
20. History of a prior non-haematologic neoplasm, except for adequately treated basal cell or squamous cell skin cancer, in situ cancer, or other cancer from which the patient has been disease free with no evidence of recurrence for ≥ 2 years.
21. Unresolved Grade ≥ 2 toxicities from prior anticancer therapies except for alopecia, vitiligo, or endocrine disorders controlled with replacement hormone therapy.
22. Active GVHD. Topical steroids for GVHD may continue indefinitely

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Incidence of DLTs during the DLT observation period.
2. Incidence, severity, and relationship to IMP, of AEs and SAEs.
3. Changes from baseline in laboratory evaluations, vital signs, physical examinations, and ECG results.
4. Duration of exposure and relative dose intensity.

Secondary endpoints 4

1. Objective Response, as assessed by the response criteria corresponding to the different haematologic neoplasms.
2. Duration of Response, Time to Response, Overall Survival, and Time to progression to AML.
3. Plasma concentrations of AZD2962.
4. Plasma PK parameters of AZD2962 (including but not limited to AUC, Cmax, and tmax, as data allow).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 1

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Urgent safety measures 1 · Art. 54 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications