AstraZeneca
The primary objective of the study is to measure efficacy of saruparib (AZD5305) plus camizestrant compared with physician's choice CDK4/6i plus ET in patients with BRCA1, BRCA2, or PALB2m, HR-positive, HER2-negative (defined as IHC 0, 1+, 2+/ ISH non-amplified) advanced breast cancer
Approximately 4680 participants will be screened to achieve approximately 788 participants randomised to study intervention. Participants will be randomised in a 2:2:1:2 ratio to one of the following intervention groups: * Arm 1: saruparib (AZD5305) plus camizestrant * Arm 2: Physician's choice CDK4/6i plus physician's choice ET * Arm 3: Physician's choice CDK4/6i plus camizestrant * Arm 4: Saruparib (AZD5305) plus physician's choice ET Treatment continues until BICR-confirmed disease progression, unacceptable toxicity occurs, or the participant withdraws consent.
Inclusion Criteria: * Adult females, pre/peri-menopausal and/or post-menopausal, and adult males * Histologically or cytologically documented diagnosis of HR-positive, HER2-negative breast cancer * Advanced breast cancer with either locally advanced disease not amenable to curative treatment or metastatic disease * ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks * FFPE tumour tissue from each participant * Documented germline tumour loss of function mutation in BRCA1, BRCA2, or PALB2 * Adequate organ and marrow function Exclusion Criteria: * Participants wi…
Saruparib (AZD5305) is a potent and selective inhibitor of PARP1, with minimal effect on PARP2.
Camizestrant (AZD9833) is an orally bioavailable, next generation SERD with non-clinical and clinical activity in both ESR1 mutant and wild type settings .
CDK4/6 Inhibitor
CDK4/6 Inhibitor
CDK 4/6 Inhibitor
Endocrine Therapy
Endorcine Therapy
Endocrine Therapy
Endocrine Therapy