Spots Global Cancer Trial Database for Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies

Study Description

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 490 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 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.

Keywords

Eligibility

Minimum Age: 18 Years

Eligible Ages: ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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