Recruiting
Phase 3

Saruparib & Camizestrant

Sponsor:

AstraZeneca

Code:

NCT06380751

Conditions

Advanced Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Saruparib (AZD5305)

Camizestrant

Abemaciclib

Ribociclib

Palbociclib

Study Details

Brief 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

Conditions

Advanced Breast Cancer

Study ID

NCT06380751

Start date

Aug 1, 2024

Status verified date

Aug, 2026

Completion date

Dec 30, 2031

Anticipated

Primary completion date

Dec 18, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

788 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm 1: saruparib (AZD5305) plus camizestrant

participants will receive saruparib (AZD5305) orally and camizestrant orally

active comparator: Arm 2: Physician's choice CDK4/6i plus physician's choice ET

agents are indicated below and should follow local guidelines:

  • Physician's Choice CDK4/6i:

  • abemaciclib orally, or
  • ribociclib orally, or
  • palbociclib orally.
  • Physician's Choice ET:

  • fulvestrant intramuscularly, or
  • One of the following AIs:

  • letrozole orally, or
  • anastrozole orally, or
  • exemestane orally

experimental: Arm 3: Physician's choice CDK4/6i plus camizestrant

participants will receive camizestrant orally. Agents for CDK4/6i treatment are indicated above and should follow local guidelines

experimental: Arm 4: Saruparib (AZD5305) plus physician's choice ET

participants will receive Saruparib (AZD5305) plus -Physician's Choice ET:

  • fulvestrant intramuscularly, or
  • One of the following AIs:

  • letrozole orally, or
  • anastrozole orally, or
  • exemestane orally

Interventions

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

Primary outcome measure

  • Progression-Free Survival (Arm 1 vs arm 2) [ Time Frame: Up to approximately 64 months ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

Locations

Research Site

Recruiting

Gilbert, Arizona, United States, 85234

Research Site

Recruiting

Fountain Valley, California, United States, 92708

Research Site

Recruiting

Glendale, California, United States, 91206

Research Site

Recruiting

Los Angeles, California, United States, 90089

Research Site

Recruiting

Newport Beach, California, United States, 92663

Research Site

Recruiting

Aurora, Colorado, United States, 80045

Research Site

Recruiting

Hollywood, Florida, United States, 33021

Research Site

Recruiting

Jacksonville, Florida, United States, 32224

Research Site

Recruiting

Arlington Heights, Illinois, United States, 60005

Research Site

Recruiting

Chicago, Illinois, United States, 60611

Research Site

Recruiting

Evanston, Illinois, United States, 60201

Research Site

Recruiting

Urbana, Illinois, United States, 61801

Research Site

Recruiting

Winfield, Illinois, United States, 60190

Research Site

Recruiting

Silver Spring, Maryland, United States, 20904

Research Site

Recruiting

Boston, Massachusetts, United States, 02215

Research Site

Recruiting

Royal Oak, Michigan, United States, 48073

Research Site

Recruiting

Rochester, Minnesota, United States, 55905

Research Site

Recruiting

Saint Joseph, Missouri, United States, 64507

Research Site

Recruiting

Springfield, Missouri, United States, 65804

Research Site

Recruiting

Camden, New Jersey, United States, 08103

Research Site

Recruiting

Mineola, New York, United States, 11501

Research Site

Recruiting

New York, New York, United States, 10016

Research Site

Recruiting

New York, New York, United States, 10065

Research Site

Recruiting

Stony Brook, New York, United States, 11790

Research Site

Recruiting

Hershey, Pennsylvania, United States, 17033

Research Site

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Research Site

Recruiting

Pittsburgh, Pennsylvania, United States, 15215

Research Site

Recruiting

Chattanooga, Tennessee, United States, 37404

Research Site

Recruiting

Nashville, Tennessee, United States, 37203

Research Site

Recruiting

Houston, Texas, United States, 77030

Research Site

Recruiting

Houston, Texas, United States, 77054

Research Site

Recruiting

San Antonio, Texas, United States, 78240

Research Site

Recruiting

Norfolk, Virginia, United States, 23502

Research Site

Recruiting

Tacoma, Washington, United States, 98405

Research Site

Recruiting

Morgantown, West Virginia, United States, 26506

More Information

Sponsor

AstraZeneca

Last update posted

Sep 2, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-09-02.