Saruparib (AZD5305) Plus Camizestrant or Plus Endocrine Therapy, 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
Recruiting
Phase 3Interventional Study
Advanced Breast Cancer
No Placebo Group
Every participant receives an active treatment — no one gets a placebo.
Pivotal Trial
This treatment is in the last trial phase before FDA approval.
Prior Safety Data
This treatment has already been tested in at least one earlier human trial.
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At a Glance
Age
18 and older
Sex
Any
Trial phase
Phase 3
Study type
Interventional
Purpose
Treatment
Participants needed
788 (estimated)
Sponsor
AstraZeneca · Industry
Who this trial is looking for
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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
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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 met…
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.
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