Saruparib (AZD5305) plus Camizestrant compared with CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant in HR-Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH non-amplified), BRCA1, BRCA2, or PALB2m Advanced Breast Cancer - EvoPAR-BR01

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 up to 28 days 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:
• (a) Strong and moderate CYP3A4 inducers/inhibitors
• (b) Sensitive CYP2B6 substrates
• (c) Substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index, eg, warfarin (and other coumarin-derived vitamin K antagonist anticoagulants) and phenytoin.
• - 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:
• (a) Disease progression ≤ 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy
• (b) Disease progression ≤ 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer
• (c) Disease progression ≤ 1 year (365 days) from the last dose with a CDK4/6i in the adjuvant setting
• (d) Disease progression ≤ 1 year (365 days) from the last dose of an oral SERD including camizestrant.