Study 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

NCT07155226 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: D8620C000012025-521299-76-00
• Study Type: interventional
• Target: 84
• Locations: 9 countries
• Sites: 30

Brief Summary

The purpose of this study is to understand the safety, tolerability, efficacy, pharmacokinetic (PK), pharmacodynamic (PD), and preliminary efficacy of orally administered AZD3632 in participants with advanced haematologic malignancies with KMT2Ar, NPM1m, or other genotypes associated with homeobox (HOX) overexpression.

Conditions

Acute Lymphoblastic Leukaemia; Higher-risk Myelodysplastic Syndromes; Acute Myeloid Leukaemia

Keywords

Myelodysplastic Syndromes; Menin inhibitor; Anti-leukaemic activity; Anti-fungal agent; HOX overexpression.

Outcome Measures

Primary Outcomes (3)

• Module 1: Number of participants with dose-limiting toxicity (DLT)

  Safety and tolerability of AZD3632 monotherapy in participants with advanced haematologic malignancies will be assessed.

  At the end of Cycle 1 (each cycle is 28 days)

• Module 1 and Module 2: Number of participants with dose modification, delay and discontinuations due to adverse events (AEs)

  Safety and tolerability of AZD3632 monotherapy in participants with advanced haematologic malignancies will be assessed.

  Up to 3 years 1 month

• Module 1 and Module 2: Number of participants with treatment-emergent adverse events (TEAEs), treatment-related AEs (TRAEs) and serious adverse vents (SAEs)

  Safety and tolerability of AZD3632 monotherapy in participants with advanced haematologic malignancies will be assessed. Adverse events will be defined as treatment-emergent if they have an onset or worsen (by investigator report of a change in intensity) during the study treatment or the safety follow-up period but prior to any subsequent cancer therapy.

  Up to 30 days after last dose (approximately 3 years 1 month)

Secondary Outcomes (29)

• Module 1 and Module 2: Maximum concentration (Cmax) of AZD3632

  From Day 1 to 3 years 1 month

• Module 1 and Module 2: Time of maximum concentration (Tmax) of AZD3632

  From Day 1 to 3 years 1 month

• Module 1: Trough concentration (Ctrough) of AZD3632

  From Day 1 to 3 years 1 month

• Module 1: Area under the plasma concentration-time Curve from Time Zero to Infinity (AUC[inf]) of AZD3632

  From Day 1 to 3 years 1 month

• Module 1 and Module 2: Area under the curve from time 0 to the time of last measurable concentration (AUC[0-t]) of AZD3632

  From Day 1 to 3 years 1 month

Study Arms (7)

Module 1: AZD3632 dose 1

EXPERIMENTAL

Participants will receive AZD3632 (dose 1) through the treatment period.

Drug: AZD3632

Module 1: AZD3632 dose 2

EXPERIMENTAL

Participants will receive AZD3632 (dose 2) through the treatment period.

Drug: AZD3632

Module 1: AZD3632 dose 3

EXPERIMENTAL

Participants will receive AZD3632 (dose 3) through the treatment period.

Drug: AZD3632

Module 1: AZD3632 dose 4

EXPERIMENTAL

Participants will receive AZD3632 (dose 4) through the treatment period.

Drug: AZD3632

Module 1: AZD3632 dose 5

EXPERIMENTAL

Participants will receive AZD3632 (dose 5) through the treatment period.

Drug: AZD3632

Module 1: AZD3632 dose 6

EXPERIMENTAL

Participants will receive AZD3632 (dose 6) through the treatment period.

Drug: AZD3632

Module 2: AZD3632 + posaconazole

EXPERIMENTAL

Participants will receive AZD3632 alone, then will receive AZD3632 in combination with posaconazole through treatment period.

Drug: AZD3632; Drug: Posaconazole

Interventions

AZD3632 DRUG

AZD3632 will be administered orally.

Module 1: AZD3632 dose 1; Module 1: AZD3632 dose 2; Module 1: AZD3632 dose 3; Module 1: AZD3632 dose 4; Module 1: AZD3632 dose 5; Module 1: AZD3632 dose 6; Module 2: AZD3632 + posaconazole

Posaconazole DRUG

Posaconazole will be administered orally.

Module 2: AZD3632 + posaconazole

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (30)

Research Site

Decatur, Illinois, 62526, United States

RECRUITING

Research Site

New York, New York, 10065, United States

NOT YET RECRUITING

Research Site

Chapel Hill, North Carolina, 27599, United States

NOT YET RECRUITING

Research Site

Durham, North Carolina, 27705, United States

RECRUITING

Research Site

Portland, Oregon, 97239, United States

NOT YET RECRUITING

Research Site

Houston, Texas, 77030, United States

RECRUITING

Research Site

Fitzroy, 3065, Australia

SUSPENDED

Research Site

Perth, WA 6000, Australia

SUSPENDED

Research Site

Toronto, Ontario, M5G 2M9, Canada

SUSPENDED

Research Site

Montreal, Quebec, H3T 1E2, Canada

SUSPENDED

Research Site

Copenhagen, 2100, Denmark

RECRUITING

Research Site

Dresden, 01307, Germany

RECRUITING

Research Site

Frankfurt A. Main, 60590, Germany

RECRUITING

Research Site

Halle, 06097, Germany

RECRUITING

Research Site

Heidelberg, 69120, Germany

RECRUITING

Research Site

München, 81377, Germany

RECRUITING

Research Site

Ulm, 89081, Germany

RECRUITING

Research Site

Bologna, 40138, Italy

RECRUITING

Research Site

Ravenna, 48121, Italy

RECRUITING

Research Site

Bunkyō City, 113-8677, Japan

RECRUITING

Research Site

Kashiwa, 277-8577, Japan

NOT YET RECRUITING

Research Site

Okayama, 700-8558, Japan

RECRUITING

Research Site

Seoul, 06351, South Korea

RECRUITING

Research Site

Seoul, 06591, South Korea

RECRUITING

Research Site

Seoul, 110-744, South Korea

RECRUITING

Research Site

Edinburgh, EH4 2XU, United Kingdom

RECRUITING

Research Site

London, EC1A 7BE, United Kingdom

NOT YET RECRUITING

Research Site

London, SE5 9RS, United Kingdom

RECRUITING

Research Site

Manchester, M20 4BX, United Kingdom

RECRUITING

Research Site

Newcastle, NE7 7DN, United Kingdom

SUSPENDED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

posaconazole

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2025
• First Posted: September 4, 2025
• Study Start: January 9, 2026
• Primary Completion (Estimated): February 15, 2029
• Study Completion (Estimated): February 15, 2029
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitment a made to the EFPIA PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: 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.

Locations

DE (6); GB (5); IT (2); KR (3); JP (3); DK (1); US (6); CA (2); AU (2)