EvoPAR-Breast01: This study is measuring the efficacy of saruparib targeted therapy plus camizestrant hormone therapy compared to other targeted therapy and hormone therapy combinations in people with BRCA1, BRCA2 or PALB2 mutations, HR+, HER2- advanced breast cancerA Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant 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

Exclusion

• 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:

  1. Strong and moderate CYP3A4 inducers/inhibitors
  2. Sensitive CYP2B6 substrates
  3. 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:

  1. Disease progression ≤ 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy
  2. Disease progression ≤ 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer
  3. Disease progression ≤ 1 year (365 days) from the last dose with a CDK4/6i in the adjuvant setting
  4. Disease progression ≤ 1 year (365 days) from the last dose of an oral SERD including camizestrant.