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
Conditions: Advanced Breast Cancer
Eligibility Criteria
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 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:
- Strong and moderate CYP3A4 inducers/inhibitors
- Sensitive CYP2B6 substrates
- 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
- Disease progression ≤ 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy
- Disease progression ≤ 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer
- Disease progression ≤ 1 year (365 days) from the last dose with a CDK4/6i in the adjuvant setting
- Disease progression ≤ 1 year (365 days) from the last dose of an oral SERD including camizestrant.
Eligibility criteria are kept as the original English records from ClinicalTrials.gov; actual eligibility is determined by the research team's formal assessment and the informed consent form. Source: ClinicalTrials.gov, updated automatically every two weeks. Last synced: 2026年10月8日.