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)
AstraZeneca
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.
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-…
Eligibility
- Age range
- 18–130 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * 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) Histologicall…
Interventions
- DrugAZD9574
Participants will receive AZD9574 orally.
- DrugTemozolomide (TMZ)
Participants will receive temozolomide orally.
- Drug[11C]AZ1419 3391
Participants will receive \[11C\]AZ1419 3391 intravenously.
- DrugTrastuzumab Deruxtecan (T-DXd)
Participants will receive T-DXd intravenously.
- DrugDatopotamab Deruxtecan (Dato-DXd)
Participants will receive Dato-DXd intravenously.
Locations (32)
- Research SiteLa Jolla, California
- Research SiteLos Angeles, California
- Research SiteSan Francisco, California
- Research SiteChicago, Illinois
- Research SiteBoston, Massachusetts
- Research SiteNew York, New York