Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies

Recruiting now · Phase 1/Phase 2

Conditions studied: Advanced Solid Malignancies

In brief

This study will assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of AZD9574 individually and in combination with anti-cancer agents in participants with advanced cancer that has recurred/progressed.

Key facts

Study ID: NCT05417594
Run by: AstraZeneca
People needed: 695
Starts: 2022-06-24
Expected to finish: 2027-11-01
Last updated by the study team: 2026-07-07

Who can join

Age: 18 and older, up to 130. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Eastern Cooperative Oncology Group performance status (ECOG PS) with no deterioration over the previous 2 weeks.
Progressive cancer at the time of enrollment.
Adequate organ and marrow function.
Module 1:
Part A:
Participants must have one of the following: (i) Histologically or cytologically confirmed relapsed advanced ovarian, fallopian tube or primary peritoneal cancer and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C or RAD51D (ii) Histologically or cytologically confirmed HER2-negative carcinoma of the breast with recurrent locally advanced or metastatic disease and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
(iii) Histologically or cytologically confirmed advanced/metastatic castration-resistant prostate cancer (CRPC) and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes:BRCA1, BRCA2, PALB2, RAD51C, or RAD51D (d) Histologically or cytologically confirmed advanced/metastatic pancreatic cancer and evidence of a predicted loss of function germline or tumour mutation in one of the following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
Must have evaluable disease.
Must be suitable for treatment with a PARPi.
Must be capable of eating a high fat meal and adhering to fasting restrictions.
Part B:
Must have metastatic or recurrent locally advanced histologically or cytologically confirmed Human Epidermal growth factor Receptor 2 (HER2)-negative carcinoma of the breast and evidence of a predicted loss of function germline or tumour mutation.
Must have at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter.
Participants who have received platinum chemotherapy for advanced breast cancer are eligible to enter the study provided there has been no evidence of disease progression during the platinum chemotherapy.
Participants who have received prior platinum-based chemotherapy as neo-adjuvant/adjuvant treatment are eligible provided at least 12 months have elapsed between the last dose of platinum-based treatment and first dose of study intervention.
Module 2:
Must be suitable for treatment with TMZ and have IDH1/2-mutant glioma.
Should have progressive disease after prior radiation therapy and one prior line of alkylating chemotherapy for their disease.
Recurrent disease must be evaluable by MRI.
Female participants of childbearing potential (CBP) must have a negative pregnancy test result at screening and prior to each cycle administration of AZD9574 and TMZ.
Adequate organ and marrow function.
Module 3:
Panel 1
Must consent to provide mandated blood samples and archival/fresh tumour tissue for confirmatory tests of their cancer using central laboratory.
Participants must have one of the following:

You may not qualify if…

Major surgery within 4 weeks of the first dose of study intervention.
Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study intervention.
With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study intervention.
Any known history of persisting severe pancytopenia due to any cause.
Spinal cord compression unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 4 weeks prior to start of study intervention.
History of uncontrolled seizures or with need for concurrent administration of more than 2 antiepileptic drugs, or history of epileptic disorder or any seizure history unrelated to tumour.
History of severe brain injury or stroke.
Any evidence of severe or uncontrolled systemic diseases including active bleeding diatheses, active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
Uncontrolled intercurrent illness within the last 12 months.
Any known predisposition to bleeding.
Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9574.
Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
Known contra-indication to gadolinium-enhanced Magnetic Resonance Imaging (MRI) or, if applicable, not able to be maintained on a stable or decreasing dose of corticosteroid regimen (no increase for 7 days) prior to the baseline MRI.
Any concurrent anti-cancer therapy or concurrent use of prohibited medications.
Module 1:
Part A:
Have received > one prior line of therapy in any setting with a PARPi-based regimen.
Participants with an INR >1.5 unless the patient is receiving non-vitamin K antagonist oral anticoagulants.
Participants with leptomeningeal disease (LMD) unless the LMD is of low volume or is previously treated and the participant is asymptomatic or minimal symptoms.
Participants with insulin-dependent diabetes.
Currently on ARA treatment.
Part B:
Participants with an International Normalised Ratio (INR) >1.5 unless the patient is receiving non-vitamin K antagonist oral anticoagulants.
Participants with LMD are excluded unless the LMD is of low volume or is previously irradiated and the participant is asymptomatic from the LMD.

Where it is running

Research Site — Sant Cugat del Vallès, Spain (enrolling)
Research Site — Seville, Spain (enrolling)
Research Site — Lund, Sweden (enrolling)
Research Site — Stockholm, Sweden (enrolling)
Research Site — Glasgow, Scotland, United Kingdom (enrolling)
Research Site — London, United Kingdom (enrolling)
Research Site — Newcastle upon Tyne, United Kingdom (enrolling)
Research Site — Los Angeles, California, United States (enrolling)
Research Site — Houston, Texas, United States (enrolling)
Research Site — San Antonio, Texas, United States (enrolling)
Research Site — San Francisco, California, United States (enrolling)
Research Site — Darlinghurst, Australia (enrolling)
Research Site — Melbourne, Australia (enrolling)
Research Site — Randwick, Australia (enrolling)
Research Site — Chicago, Illinois, United States (enrolling)
Research Site — Boston, Massachusetts, United States (enrolling)
Research Site — New York, New York, United States (enrolling)
Research Site — New York, New York, United States (enrolling)
Research Site — Seoul, South Korea (enrolling)
Research Site — Seoul, South Korea (enrolling)
Research Site — Seoul, South Korea (enrolling)
Research Site — A Coruña, Spain (enrolling)
Research Site — Barcelona, Spain (enrolling)
Research Site — Málaga, Spain (enrolling)
Research Site — Pozuelo de Alarcón, Spain (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.