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AZD3632, alone or with other anticancer agents, for advanced blood cancers driven by HOX overexpression

A Modular Phase I/II, Open-label, Multi-Centre Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of AZD3632 Monotherapy or in Combination With Anticancer Agents in Participants With Advanced Haematologic Malignancies With KMT2Ar, NPM1m, or Other Genotypes Associated With HOX Overexpression

Phase1; Phase2 Interventional AstraZeneca · NCT07155226

This trial will test whether the oral drug AZD3632, given alone or with the antifungal posaconazole, is safe and helps control relapsed or refractory AML, ALL, or high-risk MDS that have KMT2A rearrangements, NPM1 mutations, or other genotypes causing HOX overexpression.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment84 (estimated)
Ages16 Years and up
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionschemotherapy, radiation
Locations30 sites (Decatur, Illinois and 29 other locations)
Trial IDNCT07155226 on ClinicalTrials.gov

What this trial studies

This is a first‑in‑human, open‑label, multi‑center study enrolling adults with relapsed or refractory acute leukaemia or higher‑risk myelodysplastic syndromes whose tumors show HOX overexpression genotypes. The program is organized into modules: module 1 performs dose escalation of AZD3632 as monotherapy, and module 2 studies safety, PK, and tolerability when AZD3632 is co‑administered with posaconazole. Key outcomes include safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti‑leukaemic activity. Participants must have measurable disease, adequate organ function, and relevant genetic alterations such as KMT2A rearrangements or NPM1 mutations.

Who should consider this trial

Good fit: Adults with relapsed or refractory AML, ALL, or higher‑risk MDS who have measurable disease, adequate organ function, and a KMT2A rearrangement, NPM1 mutation, or other genotype associated with HOX overexpression are the intended candidates.

Not a fit: Patients whose cancers do not show HOX overexpression, who have effective approved therapies available, or who cannot meet organ function or contraception requirements are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, AZD3632 could provide a new targeted oral treatment option that reduces disease burden for patients with HOX‑driven blood cancers.

How similar studies have performed: Other menin inhibitors have shown promising preclinical activity and early clinical responses in KMT2A‑rearranged and NPM1‑mutant leukemias, but AZD3632 is being tested here in a first‑in‑human program.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

Core criteria:

* Adequate organ function.
* Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Module 1:

* Advanced haematologic malignancy - a) for dose escalation - diagnosis of acute leukemia or myelodysplastic neoplasia (MDS) and harbouring one of the genetic alterations per local testing associated with upregulation of HOX; b) for Backfill - diagnosis of harbouring a KMT2Ar or NPM1m per local testing.
* Participants must have measurable disease that is relapsed/refractory to conventional therapies known to be effective for their disease and not have any available approved therapies.: a) Relapsed and primary refractory acute leukaemia after standard of care therapy including but not limited to 2 cycles of intensive chemotherapy, hypomethylating agent (HMA) monotherapy, or HMA combinations such as HMA/venetoclax.; b) Relapsed and primary refractory MDS is defined by ≥ 5% blasts in the bone marrow and/or persistence of peripheral blasts after treatment with at least 2 cycles of HMA. Participants ineligible for the treatment with an HMA and without any other standard of care (SoC) options are allowed to enrol; c) White blood cell count below 25,000/μL. Participants may receive cytoreduction per protocol-specified criteria; d) Performance status: Eastern Cooperative Operative Group (ECOG) ≤ 2; e) Life expectancy: ≥ 8 weeks.

Module 2:

* Participants must have measurable disease that is relapsed/refractory to conventional therapies known to be effective for their disease and not have any available approved therapies.: a) Relapsed and primary refractory acute leukaemia after standard of care therapy including but not limited to 2 cycles of intensive chemotherapy, HMA monotherapy, or HMA combinations such as HMA/venetoclax.; b) Relapsed and primary refractory MDS is defined by ≥ 5% blasts in the bone marrow and/or persistence of peripheral blasts after treatment with at least 2 cycles of HMA. Participants ineligible for the treatment with an HMA and without any other SoC options are allowed to enrol; c) White blood cell count below 25,000/μL. Participants may receive cytoreduction per protocol-specified criteria; d) Performance status: ECOG ≤ 2; e) Life expectancy: ≥ 8 weeks.

Key Exclusion Criteria:

Core criteria:

* Participants with Burkitt lymphoma/leukaemia or Acute Promyelocytic Leukaemia.
* Active testicular or active central nervous system (CNS) (\> CNS1 or radiographic) involvement by leukaemia.
* Unresolved treatment-related toxicities Grade ≥ 2 from prior therapy.
* Abnormal levels of potassium or magnesium prior to first dose of AZD3632.

Module 1:

* Receipt of non-CNS radiation therapy within 2 weeks and of CNS radiation within 8 weeks of the first scheduled dose.
* Receipt of any investigational or non-investigational anticancer agents, including non-biologic agents, biologic agents and/or prior treatment other menin inhibitors (backfill participants only).
* For nested food effect participants - diagnosis of diabetes mellitus (Type I or Type II).

Module 2:

* Receipt of any non-investigational anticancer agents, including non-biologic agents and/or biologic agents or receipt of non-CNS or CNS radiation therapy.
* Participants for whom treatment with posaconazole is contraindicated per the local prescribing information.

Where this trial is running

Decatur, Illinois and 29 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Acute Lymphoblastic LeukaemiaAcute Myeloid LeukaemiaHigher-risk Myelodysplastic SyndromesMyelodysplastic SyndromesMenin inhibitorAnti-leukaemic activityAnti-fungal agentHOX overexpression.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.