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.

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.

Key Inclusion Criteria:

1. 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.
2. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
3. Participants must have symptomatic disease that requires therapy and allows for objective efficacy assessments.
4. Willing to provide baseline bone marrow aspirate (or biopsy if dry-tap).
5. Contraceptive use by participants or participant partners should be consistent with local regulations and also comply with Clinical Study Protocol requirements.
6. All women of childbearing potential must have a negative serum pregnancy test result at Screening.

Key Exclusion Criteria:

1. Prior treatment with IRAK inhibitors or inhibitors of the inflammasome pathway.
2. Received any antineoplastic therapy (except hydroxyurea) within 15 days prior to first dose.
3. Received any strong or moderate Cytochrome P450 3A (CYP3A) inhibitors within 15 days prior to first dose.
4. Received major surgery within 28 days prior to first dose, or still recovering from surgery.
5. 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.
6. 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).
7. Received live attenuated vaccines within 28 days prior to first dose.
8. Active major bleeding event.
9. 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.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.