A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant or Plus Endocrine Therapy, Compared With Physician's Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients With BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified) Advanced Breast Cancer (EvoPAR-Breast01)
A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant or Plus Endocrine Therapy, Compared With Physician's Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients With BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified) Advanced Breast Cancer (EvoPAR-Breast01)
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:
Treatment continues until BICR-confirmed disease progression, unacceptable toxicity occurs, or the participant withdraws consent.
Inclusion Criteria:
Exclusion Criteria:
Participants with history of MDS/AML or with features suggestive of MDS/AML
Participants with any known predisposition to bleeding
Any history of persisting severe cytopenia
Any evidence of severe or uncontrolled systemic diseases or active uncontrolled infections
Refractory nausea and vomiting, chronic GI disease, inability to swallow the formulated product, or previous significant bowel resection
History of another primary malignancy
Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anti-cancer therapy excluding alopecia
Spinal cord compression, brain metastases, carcinomatous meningitis, or leptomeningeal disease
Evidence of active and uncontrolled hepatitis B and/or hepatitis C
Evidence of active and uncontrolled HIV infection
Active tuberculosis infection
Cardiac criteria, including history of arrythmia and cardiovascular disease
Concurrent exogenous reproductive hormone therapy or non-topical hormonal therapy for non-cancer-related conditions
Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study
Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks before the first dose of study treatment
Prior treatment with systemic anti-cancer therapy for locoregionally recurrent or metastatic disease is not permitted, apart from treatment with ET for up to 28 days total before randomisation
Prior treatment within 28 days with blood product support or growth factor support
Any systemic concurrent anti-cancer treatment
Concomitant use of the following types of medications or herbal supplements within 21 days or at least 5 half-lives of randomisation:
Concomitant use of drugs that are known to prolong QT and have a known risk of TdP
Systemic use of atropine
The following exclusion criteria apply to treatments administered for early breast cancer:
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