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NCT07155226PHASE1, PHASE2Recruiting

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

AstraZeneca

Start Date

1/9/2026

Completion Date

2/15/2029

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.

Detailed Description

This is a first in human (FTiH), open-label, multi-centre study of AZD3632 in participants with relapsed or refractory acute leukaemia or myelodysplastic Syndromes (MDS) with HOX overexpression genotypes. This study includes multiple modules (module 1 and module 2) each investigating AZD3632 in a specific population and/or in combination with other anticancer agents. Module 1 is a dose escalation of AZD3632 monotherapy. Module 2 will investigate the safety, PK, and tolerability when co-administered with posaconazole.

Eligibility Criteria

Age Range: 16 years to No maximum

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.

Interventions

DRUG

AZD3632

DRUG

Posaconazole

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Conditions

Acute Lymphoblastic LeukaemiaAcute Myeloid LeukaemiaHigher-risk Myelodysplastic Syndromes

Locations

Research Site

Decatur, Illinois 62526

United States

Research Site

New York, New York 10065

United States

Research Site

Chapel Hill, North Carolina 27599

United States

Research Site

Durham, North Carolina 27705

United States

Research Site

Portland, Oregon 97239

United States

Research Site

Houston, Texas 77030

United States

Research Site

Fitzroy, 3065

Australia

Research Site

Perth, WA 6000

Australia

Research Site

Toronto, Ontario M5G 2M9

Canada

Research Site

Montreal, Quebec H3T 1E2

Canada

Research Site

Copenhagen, 2100

Denmark

Research Site

Dresden, 01307

Germany

Research Site

Frankfurt A. Main, 60590

Germany

Research Site

Halle, 06097

Germany

Research Site

Heidelberg, 69120

Germany

Research Site

München, 81377

Germany

Research Site

Ulm, 89081

Germany

Research Site

Bologna, 40138

Italy

Research Site

Ravenna, 48121

Italy

Research Site

Bunkyō City, 113-8677

Japan

Research Site

Kashiwa, 277-8577

Japan

Research Site

Okayama, 700-8558

Japan

Research Site

Seoul, 06351

South Korea

Research Site

Seoul, 06591

South Korea

Research Site

Seoul, 110-744

South Korea

Research Site

Edinburgh, EH4 2XU

United Kingdom

Research Site

London, EC1A 7BE

United Kingdom

Research Site

London, SE5 9RS

United Kingdom

Research Site

Manchester, M20 4BX

United Kingdom

Research Site

Newcastle, NE7 7DN

United Kingdom