Study identifier:D8410C00001
ClinicalTrials.gov identifier:NCT05417594
EudraCT identifier:2021-006227-17
CTIS identifier:2023-504984-17-00
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)
Advanced solid malignancies
Phase 1/2
No
AZD9574, Temozolomide, [11C]AZ1419 3391, Datopotamab Deruxtecan (Dato-DXd), Trastuzumab Deruxtecan (T-DXd)
All
490
Interventional
18 Years - 130 Years
Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment
Verified 01 Nov 2024 by AstraZeneca
AstraZeneca
-
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 490 participants with advanced cancer that has recurred/progressed.
This is a modular phase I/IIa, multi-centre, multi-part, open-label, dose escalation, and dose expansion study. Approximately 490 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 220 participants: - Part A (dose-escalation cohorts) will include 130 participants (including backfills) 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 BRCA mutated (BRCA1m, and BRCA2m), PALB2 mutation (PALB2m), RAD51Cm or RAD51Dm, without evidence of 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): - Part A (dose-escalation cohorts) will include 75 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 90 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) may be added in the future following a protocol amendment. • Module 5 (AZD9574 in combination with Datopotamab deruxtecan [Dato-DXd]) This module will include 90 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.
No locations available
Arms | Assigned Interventions |
---|---|
Experimental: Module 1 Part A: Dose escalation Participants with advanced/relapsed ovarian, breast, pancreatic, or prostate cancer who are deemed suitable for a PARPi will receive AZD9574 monotherapy at escalating cohorts. | Drug: AZD9574 Participants will receive AZD9574 orally. |
Experimental: Module 1 Part B: Dose expansion Participants with breast cancer who are PARPi naive at doses determined in dose-escalation. | Drug: AZD9574 Participants will receive AZD9574 orally. |
Experimental: Module 2 Part A: Dose escalation Participants with IDH 1/2-mutant glioma who are PARPi naive will receive AZD9574 and TMZ at escalating cohorts. | Drug: AZD9574 Participants will receive AZD9574 orally. Drug: Temozolomide Participants will receive temozolomide orally. |
Experimental: Module 3 Panel 1: AZD9574 monotherapy (Sweden only) Participants with advanced/relapsed HER2-negative breast, ovarian, prostate, or pancreatic cancer and expressing BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm. | Drug: [11C]AZ1419 3391 Participants will receive [11C]AZ1419 3391 intravenously. |
Experimental: Module 3 Panel 2: AZD9574 + TMZ (Sweden only) Participants with IDH 1/2-mutant glioma who are PARPi naive will receive AZD9574 and TMZ at escalating cohorts. | Drug: [11C]AZ1419 3391 Participants will receive [11C]AZ1419 3391 intravenously. |
Experimental: Module 3 Panel 3: AZD9574 monotherapy (Sweden only) Participants with breast cancer (without BM). | Drug: [11C]AZ1419 3391 Participants will receive [11C]AZ1419 3391 intravenously. |
Experimental: Module 4 Part A: Dose escalation (AZD9574 + T-DXdat) Participants with advanced, unresectable, or metastatic solid tumours that are HER2-positive will receive a combination of AZD9574 and T-DXdat at escalating cohorts. | Drug: AZD9574 Participants will receive AZD9574 orally. Drug: Trastuzumab Deruxtecan (T-DXd) Participants will receive T-DXd intravenously. |
Experimental: Module 5 Part A : Dose escalation (AZD9574 + Dato-DXd) Participants with advanced, unresectable, or metastatic solid tumours in different types of cancers will receive a combination of AZD9574 and Dato-DXd at escalating cohorts. | Drug: AZD9574 Participants will receive AZD9574 orally. Drug: Datopotamab Deruxtecan (Dato-DXd) Participants will receive Dato-DXd intravenously. |