Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies — CERTIS1  

Advanced Solid Malignancies Clinical Trial

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

Clinical Trial 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 490 participants with advanced cancer that has recurred/progressed.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Advanced Solid Malignancies
• Neoplasms

• NCT number: NCT05417594
• Study type: Interventional
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center@astrazeneca.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 24, 2022
• Completion date: January 12, 2026