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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. (EvoPAR-Breast01)

A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant Compared With Physician's Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients With BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified) Advanced Breast Cancer (EvoPAR-Breast01) (EvoPAR-Breast01)

Hibi Kazushige

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi

RD-clinical-information-Japan@astrazeneca.com

Hibi Kazushige

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi

+81-6-4802-3533

RD-clinical-information-Japan@astrazeneca.com

Recruiting

July. 18, 2024

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

- 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

- 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 more than 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 up to 28 days 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 less than 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy
2. Disease progression less than 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer
3. Disease progression less than 1 year (365 days) from the last dose with a CDK4/6i in the adjuvant setting
4. Disease progression less than 1 year (365 days) from the last dose of an oral SERD including camizestrant.

Both

Advanced Breast Cancer

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

Progression-Free Survival (PFS)
PFS is defined as time from randomisation until progression per RECIST v1.1 as assessed by BICR, or death due to any cause.
Time Frame; Up to approximately 59 months

+81-3-3520-0111

Yes

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

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