Ignite Creation Date:
2025-12-25 @ 1:45 AM
Ignite Modification Date:
2026-03-06 @ 7:38 AM
Study NCT ID:
NCT05417594
Status:
RECRUITING
Last Update Posted:
2025-12-22
First Post:
2022-05-20
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies
Sponsor:
AstraZeneca
Organization:
Study Overview
Official Title:
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)
Status:
RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CERTIS1
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.
Detailed Description:
This is a modular phase I/IIa, multi-centre, multi-part, open-label, dose escalation, and dose expansion study.
Approximately 695 participants will be enrolled and assigned to study treatments.
This study consists of individual modules each evaluating safety and tolerability.
* Core protocol which contains information applicable to all modules.
* Module 1 (AZD9574 monotherapy):
This module will include 235 participants:
* Part A (dose-escalation cohorts) will include participants with advanced/relapsed ovarian, breast, pancreatic or prostate cancer that are deemed suitable for a Poly ADP-Ribose Polymerase (PARPi) by the Investigator.
* Part B (dose-expansion cohorts):
This module will include up to 3 expansion cohorts with 30 participants in each:
* Cohort B1 will include participants with advanced/relapsed Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer participants with breast cancer gene (BRCA) mutated (BRCA1m, and BRCA2m), partner and localiser of the BRCA2 gene (PALB2) mutation (PALB2m), RAD51Cm or RAD51Dm, without evidence of untreated brain metastasis at baseline Magnetic Resonance Imaging (MRI) scan.
* Cohort B2 will include participants with advanced/relapsed HER2-negative breast cancer participants with BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm, who have either untreated or treated brain metastases that are not requiring immediate local therapy.
* Up to of 20 participants may be required to get 12 evaluable participants in each cohort for food effect and Acid Reducing Agent (ARA) investigations.
• Module 2 (AZD9574 in combination with temozolomide (TMZ): This module will include 75 participants for up to 12 cycles.
* Part A (dose-escalation cohorts) will include participants with Isocitrate Dehydrogenase (IDH)-mutant glioma.
• Module 3 (PET Sub-study: AZD9574 monotherapy \[Panels 1 and 3\], AZD9574 in combination with TMZ (Panel 2). This module will include 12 participants and is only applicable for Sweden.
* Panel 1 (AZD9574 monotherapy) will include up to 8 participants with advanced/relapsed HER2-negative breast, ovarian, prostate, or pancreatic cancer and expressing BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm.
* Panel 2 (AZD9574 + TMZ) will include up to 2 participants with IDH-mutant recurrent glioma.
* Panel 3 (AZD9574 monotherapy) will include up to 2 participants with breast cancer (without BM).
* Module 4 (AZD9574 in combination with Trastuzumab deruxtecan \[T-DXd\])
This module will include 265 participants (including backfills):
* Part A (dose escalation cohorts) will include participants with advanced, unresectable, or metastatic solid tumours that are HER2-positive.
* Part B (dose expansion cohorts) will include up to 4 cohorts with participants with HER2-low/ultralow, HR positive breast cancer. Approximately 30 response evaluable participants without brain metastases will be enrolled in each cohort and up to 10 additional participants with brain metastases (CNS cohort) may be enrolled in each cohort.
* Module 5 (AZD9574 in combination with Datopotamab deruxtecan \[Dato-DXd\])
This module will include 105 participants (including backfills):
* Part A (dose escalation cohorts) will include participants with advanced, unresectable, or metastatic solid tumours in different types of cancers.
* Part B (dose expansion cohorts) may be added in the future amendment.
Approximately 695 participants will be enrolled and assigned to study treatments.
This study consists of individual modules each evaluating safety and tolerability.
* Core protocol which contains information applicable to all modules.
* Module 1 (AZD9574 monotherapy):
This module will include 235 participants:
* Part A (dose-escalation cohorts) will include participants with advanced/relapsed ovarian, breast, pancreatic or prostate cancer that are deemed suitable for a Poly ADP-Ribose Polymerase (PARPi) by the Investigator.
* Part B (dose-expansion cohorts):
This module will include up to 3 expansion cohorts with 30 participants in each:
* Cohort B1 will include participants with advanced/relapsed Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer participants with breast cancer gene (BRCA) mutated (BRCA1m, and BRCA2m), partner and localiser of the BRCA2 gene (PALB2) mutation (PALB2m), RAD51Cm or RAD51Dm, without evidence of untreated brain metastasis at baseline Magnetic Resonance Imaging (MRI) scan.
* Cohort B2 will include participants with advanced/relapsed HER2-negative breast cancer participants with BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm, who have either untreated or treated brain metastases that are not requiring immediate local therapy.
* Up to of 20 participants may be required to get 12 evaluable participants in each cohort for food effect and Acid Reducing Agent (ARA) investigations.
• Module 2 (AZD9574 in combination with temozolomide (TMZ): This module will include 75 participants for up to 12 cycles.
* Part A (dose-escalation cohorts) will include participants with Isocitrate Dehydrogenase (IDH)-mutant glioma.
• Module 3 (PET Sub-study: AZD9574 monotherapy \[Panels 1 and 3\], AZD9574 in combination with TMZ (Panel 2). This module will include 12 participants and is only applicable for Sweden.
* Panel 1 (AZD9574 monotherapy) will include up to 8 participants with advanced/relapsed HER2-negative breast, ovarian, prostate, or pancreatic cancer and expressing BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm.
* Panel 2 (AZD9574 + TMZ) will include up to 2 participants with IDH-mutant recurrent glioma.
* Panel 3 (AZD9574 monotherapy) will include up to 2 participants with breast cancer (without BM).
* Module 4 (AZD9574 in combination with Trastuzumab deruxtecan \[T-DXd\])
This module will include 265 participants (including backfills):
* Part A (dose escalation cohorts) will include participants with advanced, unresectable, or metastatic solid tumours that are HER2-positive.
* Part B (dose expansion cohorts) will include up to 4 cohorts with participants with HER2-low/ultralow, HR positive breast cancer. Approximately 30 response evaluable participants without brain metastases will be enrolled in each cohort and up to 10 additional participants with brain metastases (CNS cohort) may be enrolled in each cohort.
* Module 5 (AZD9574 in combination with Datopotamab deruxtecan \[Dato-DXd\])
This module will include 105 participants (including backfills):
* Part A (dose escalation cohorts) will include participants with advanced, unresectable, or metastatic solid tumours in different types of cancers.
* Part B (dose expansion cohorts) may be added in the future amendment.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: