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
Saruparib (AZD5305): Saruparib (AZD5305) is a potent and selective inhibitor of PARP1, with minimal effect on PARP2.
Camizestrant: Camizestrant (AZD9833) is an orally bioavailable, next generation SERD with non-clinical and clinical activity in both ESR1 mutant and wild type settings .
Abemaciclib: CDK4/6 Inhibitor
Ribociclib: CDK4/6 Inhibitor
Palbociclib: CDK 4/6 Inhibitor
Fulvestrant: Endocrine Therapy
Letrozole: Endorcine Therapy
Anastrozole: Endocrine Therapy
Exemestane: Endocrine Therapy
Study summary
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
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Progression-Free Survival (Arm 1 vs arm 2) — Up to approximately 64 months PFS is defined as time from randomisation until progression per RECIST v1.1 as assessed by BICR, or death due to any cause.
Trial sites (306)
Facility
City
Region
Status
Research Site
Gilbert
Arizona
Recruiting
Research Site
Fountain Valley
California
Recruiting
Research Site
Glendale
California
Recruiting
Research Site
Los Angeles
California
Recruiting
Research Site
Newport Beach
California
Recruiting
Research Site
Aurora
Colorado
Recruiting
Research Site
Grand Junction
Colorado
Withdrawn
Research Site
Hollywood
Florida
Recruiting
Research Site
Jacksonville
Florida
Recruiting
Research Site
Orlando
Florida
Withdrawn
Research Site
Orlando
Florida
Not Yet Recruiting
Research Site
Arlington Heights
Illinois
Recruiting
Research Site
Chicago
Illinois
Recruiting
Research Site
Evanston
Illinois
Recruiting
Research Site
Park Ridge
Illinois
Withdrawn
Research Site
Schaumburg
Illinois
Not Yet Recruiting
Research Site
Urbana
Illinois
Recruiting
Research Site
Winfield
Illinois
Recruiting
Research Site
Indianapolis
Indiana
Withdrawn
Research Site
Louisville
Kentucky
Withdrawn
Research Site
Baltimore
Maryland
Not Yet Recruiting
Research Site
Silver Spring
Maryland
Withdrawn
Research Site
Silver Spring
Maryland
Recruiting
Research Site
Boston
Massachusetts
Recruiting
Research Site
Dearborn
Michigan
Withdrawn
Research Site
Detroit
Michigan
Withdrawn
Research Site
Royal Oak
Michigan
Withdrawn
Research Site
Royal Oak
Michigan
Recruiting
Research Site
Rochester
Minnesota
Recruiting
Research Site
Saint Joseph
Missouri
Recruiting
Research Site
Springfield
Missouri
Recruiting
Research Site
St Louis
Missouri
Not Yet Recruiting
Research Site
Camden
New Jersey
Recruiting
Research Site
New Brunswick
New Jersey
Withdrawn
Research Site
Brooklyn
New York
Withdrawn
Research Site
Mineola
New York
Recruiting
Research Site
New Hyde Park
New York
Withdrawn
Research Site
New York
New York
Recruiting
Research Site
New York
New York
Withdrawn
Research Site
New York
New York
Recruiting
+ 266 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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