Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies
CERTIS1
A Modular Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (CERTIS1)
3 other identifiers
interventional
695
7 countries
32
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2022
Longer than P75 for phase_1
32 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 20, 2022
CompletedFirst Posted
Study publicly available on registry
June 14, 2022
CompletedStudy Start
First participant enrolled
June 24, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 13, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 13, 2027
May 5, 2026
April 1, 2026
5.3 years
May 20, 2022
April 29, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Incidence of Adverse Events (AEs), and Serious Adverse Events (SAEs)
The safety and tolerability of AZD9574 as monotherapy and in combination with anti-cancer agents and TMZ in participants with advanced malignancies will be assessed.
From first dose to post-treatment follow-up (approximately three years)
Changes from baseline in laboratory findings, electrocardiograms (ECGs), and vital signs
The safety and tolerability of AZD9574 as monotherapy and in combination with anti-cancer agents and TMZ in participants with advanced malignancies will be assessed.
From last assessment prior to first dose to post-treatment follow up visit (approximately three years)
Change from baseline Eastern Cooperative Oncology Group performance status (ECOG PS)
The performance status of ECOG will be assessed based on an ECOG grade of 0 to 4 where '0' is a high grade while '4' is a low grade. An ECOG grade of '0' means that the participant is fully active, able to carry on all pre-disease performance without restriction. An ECOG grade of '4' means that the participant is completely disabled, cannot carry on any self-care, and is totally confined to a bed or chair.
From last assessment prior to first dose to post-treatment follow up visit (approximately three years)
Incidence of Dose Limiting Toxicities (DLTs)
The safety and tolerability of AZD9574 as monotherapy and in combination with anti-cancer agents in participants with advanced malignancies will be assessed at each dose level.
Cycle 0 and Cycle 1 (Day 1 to Day 35)
Secondary Outcomes (77)
Area Under the Curve (AUC)
Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)
Maximum plasma concentration (Cmax)
Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)
Time to reach maximum plasma concentration (tmax)
Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)
Minimum plasma concentration at steady state (Cmin,ss)
Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)
Half-life (t1/2)
Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)
- +72 more secondary outcomes
Study Arms (9)
Module 1 Part A: Dose escalation
EXPERIMENTALParticipants with advanced/relapsed ovarian, breast, pancreatic, or prostate cancer who are deemed suitable for a PARPi will receive AZD9574 monotherapy at escalating cohorts.
Module 1 Part B: Dose expansion
EXPERIMENTALParticipants with breast cancer who are PARPi naive at doses determined in dose-escalation.
Module 2 Part A: Dose escalation
EXPERIMENTALParticipants with IDH 1/2-mutant glioma who are PARPi naive will receive AZD9574 and TMZ at escalating cohorts.
Module 3 Panel 1: AZD9574 monotherapy (Sweden only)
EXPERIMENTALParticipants with advanced/relapsed HER2-negative breast, ovarian, prostate, or pancreatic cancer and expressing BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm.
Module 3 Panel 2: AZD9574 + TMZ (Sweden only)
EXPERIMENTALParticipants with IDH 1/2-mutant glioma who are PARPi naive will receive AZD9574 and TMZ at escalating cohorts.
Module 3 Panel 3: AZD9574 monotherapy (Sweden only)
EXPERIMENTALParticipants with breast cancer (without BM).
Module 4 Part A: Dose escalation (AZD9574 + T-DXd)
EXPERIMENTALParticipants with advanced, unresectable, or metastatic solid tumours that are HER2-positive will receive a combination of AZD9574 and T-DXd at at escalating cohorts.
Module 4 Part B : Dose expansion (AZD9574 + T-DXd)
EXPERIMENTALParticipants with HER2-low/ultralow, HR positive breast cancer will receive a combination of different doses of AZD9574 and T-DXd at expanding cohorts.
Module 5 Part A : Dose escalation (AZD9574 + Dato-DXd)
EXPERIMENTALParticipants with advanced, unresectable, or metastatic solid tumours in different types of cancers will receive a combination of AZD9574 and Dato-DXd at escalating cohorts.
Interventions
Participants will receive T-DXd intravenously.
Participants will receive temozolomide orally.
Participants will receive \[11C\]AZ1419 3391 intravenously.
Participants will receive AZD9574 orally.
Participants will receive Dato-DXd intravenously.
Eligibility Criteria
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.
- +78 more criteria
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.
- +75 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (32)
Research Site
La Jolla, California, 92093, United States
Research Site
Los Angeles, California, 90095, United States
Research Site
San Francisco, California, 94143, United States
Research Site
Chicago, Illinois, 60611, United States
Research Site
Boston, Massachusetts, 02215, United States
Research Site
New York, New York, 10040, United States
Research Site
New York, New York, 10065, United States
Research Site
Portland, Oregon, 97239, United States
Research Site
Houston, Texas, 77030, United States
Research Site
San Antonio, Texas, 78229, United States
Research Site
Richmond, Virginia, 23298, United States
Research Site
Darlinghurst, 2010, Australia
Research Site
Melbourne, 3000, Australia
Research Site
Randwick, 2031, Australia
Research Site
Bayern, 80337, Germany
Research Site
Berlin, 13353, Germany
Research Site
Heidelberg, 69120, Germany
Research Site
Mainz, 55131, Germany
Research Site
Seoul, 03080, South Korea
Research Site
Seoul, 03722, South Korea
Research Site
Seoul, 06351, South Korea
Research Site
A Coruña, 15006, Spain
Research Site
Barcelona, 8035, Spain
Research Site
Málaga, 29010, Spain
Research Site
Pozuelo de Alarcón, 28223, Spain
Research Site
Sant Cugat del Vallès, 08195, Spain
Research Site
Seville, 41013, Spain
Research Site
Lund, 22185, Sweden
Research Site
Stockholm, 118 83, Sweden
Research Site
Glasgow, Scotland, G12 0YN, United Kingdom
Research Site
London, EC1M 6BQ, United Kingdom
Research Site
Newcastle upon Tyne, NE7 7DN, United Kingdom
Related Publications (1)
Staniszewska AD, Pilger D, Gill SJ, Jamal K, Bohin N, Guzzetti S, Gordon J, Hamm G, Mundin G, Illuzzi G, Pike A, McWilliams L, Maglennon G, Rose J, Hawthorne G, Cortes Gonzalez M, Halldin C, Johnstrom P, Schou M, Critchlow SE, Fawell S, Johannes JW, Leo E, Davies BR, Cosulich S, Sarkaria JN, O'Connor MJ, Hamerlik P. Preclinical Characterization of AZD9574, a Blood-Brain Barrier Penetrant Inhibitor of PARP1. Clin Cancer Res. 2024 Apr 1;30(7):1338-1351. doi: 10.1158/1078-0432.CCR-23-2094.
PMID: 37967136DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
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
May 20, 2022
First Posted
June 14, 2022
Study Start
June 24, 2022
Primary Completion (Estimated)
October 13, 2027
Study Completion (Estimated)
October 13, 2027
Last Updated
May 5, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer 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 de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. 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.