Phase 3 study for people with Breast Cancer

Reproduced exactly, unedited. Written for researchers rather than for patients.

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:

  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.