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 2,620 participants will be screened to achieve approximately 500 participants randomised to study intervention. Participants will be randomised in a 2:2:1 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 Treatment continues until BICR-confirmed disease progression, unacceptable toxicity occurs, or the participant withdraws consent.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
500
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
Research Site
Gilbert, Arizona, United States
RECRUITINGResearch Site
Fountain Valley, California, United States
RECRUITINGResearch Site
Glendale, California, United States
RECRUITINGResearch Site
Los Angeles, California, United States
Progression-Free Survival
PFS is defined as time from randomisation until progression per RECIST v1.1 as assessed by BICR, or death due to any cause.
Time frame: Up to approximately 59 months
Overall Survival
OS is defined as the time from randomisation until the date of death due to any cause.
Time frame: Up to approximately 88 months
Progression Free Survival 2
PFS2 is defined as the time from randomisation to the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death.
Time frame: Up to approximately 59 months
Time to chemotherapy
Time to chemotherapy is defined as time from randomisation until the start date of the first subsequent chemotherapy treatment after discontinuation of randomised treatment (censoring participants who died prior to initiation of chemotherapy).
Time frame: Up to approximately 59 months
Objective Response Rate
ORR is defined as the proportion of participants who have a complete or parial response, as determined by BICR per RECIST v1.1.
Time frame: Up to approximately 59 months
Duration of Response
DoR is defined as the time from the date of first documented response until date of documented progression per RECIST v1.1 as assessed by BICR, or death due to any cause.
Time frame: Up to approximately 59 months
Participant-reported tolerability
Proportion of all dosed participants reporting different levels of severity of diarrhoea as measured by the diarrhoea single item (EORTC IL237/IL239/IL240) and different levels of severity of abdominal pain as measured by the abdominal pain single item (EORTC IL237/IL239/IL240).
Time frame: Up to approximately 59 months
Time to deterioration in patient-reported global health status/QoL as measured by the global health status/QoL scale within the The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)
This scale includes 2 items asking participants to report overall health and overall quality of life in the past week. Both items are measured on a 6-point verbal rating scale ranging from Very Poor to Excellent. Single item scores are averaged to calculate a subscale score that is transformed to range from 0 to 100, where higher scores indicate better global health status/QoL.
Time frame: Up to approximately 59 months
Change from baseline in patient-reported global health status/QoL as measured by the global health status/QoL scale within the The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)
This scale includes 2 items asking participants to report overall health and overall quality of life in the past week. Both items are measured on a 6-point verbal rating scale ranging from Very Poor to Excellent. Single item scores are averaged to calculate a subscale score that is transformed to range from 0 to 100, where higher scores indicate better global health status/QoL.
Time frame: Up to approximately 59 months
Plasma concentrations of saruparib (AZD5305)
Time frame: Up to approximately 59 months
Plasma concentrations of camizestrant
Time frame: Up to approximately 59 months
Samples will be used to develop companion diagnostics by analyzing their performance characteristics and calculate their consistency with clinical trial assays used for enrolment onto the study.
Samples will be tested by a CDx to confirm BRCA1/2 and PALB2 gene mutation status
Time frame: Up to approximately 59 months
AstraZeneca Clinical Study Information Center
CONTACT
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Research Site
Newport Beach, California, United States
RECRUITINGResearch Site
Aurora, Colorado, United States
RECRUITINGResearch Site
Grand Junction, Colorado, United States
WITHDRAWNResearch Site
Hollywood, Florida, United States
RECRUITINGResearch Site
Jacksonville, Florida, United States
NOT_YET_RECRUITINGResearch Site
Orlando, Florida, United States
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