Saruparib (AZD5305) plus Camizestrant 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 - EvoPAR-BR01

Study identifier:D9722C00001

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Will Be Recruiting

Official Title

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)

Medical condition

Advanced breast cancer

Phase

Phase 3

Healthy volunteers

Study drug

Saruparib (AZD5305), Camizestrant, Abemaciclib, Ribociclib, Palbociclib, Fulvestrant, Letrozole, Anastrozole, Exemestane

Sex

All

Estimated Enrollment

500

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 18 Apr 2024

Estimated Primary Completion Date: 30 Mar 2029

Estimated Study Completion Date: 18 Jul 2030

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2024 by AstraZeneca

Collaborators

Inclusion and exclusion 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 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 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:
(a) Strong and moderate CYP3A4 inducers/inhibitors
(b) Sensitive CYP2B6 substrates
(c) 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:
(a) Disease progression ≤ 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy
(b) Disease progression ≤ 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer
(c) Disease progression ≤ 1 year (365 days) from the last dose with a CDK4/6i in the adjuvant setting
(d) Disease progression ≤ 1 year (365 days) from the last dose of an oral SERD including camizestrant.

No locations available

Arms	Assigned Interventions
Experimental: Arm 1: saruparib (AZD5305) plus camizestrant participants will receive saruparib (AZD5305) orally and camizestrant orally	Drug: Saruparib (AZD5305) Saruparib (AZD5305) is a potent and selective inhibitor of PARP1, with minimal effect on PARP2. Drug: Camizestrant Camizestrant (AZD9833) is an orally bioavailable, next generation SERD with non-clinical and clinical activity in both ESR1 mutant and wild type settings .
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: o abemaciclib orally, or o ribociclib orally, or o palbociclib orally. -Physician's Choice ET: o fulvestrant intramuscularly, or o One of the following AIs: •letrozole orally, or •anastrozole orally, or •exemestane orally	Drug: Abemaciclib CDK4/6 Inhibitor Drug: Ribociclib CDK4/6 Inhibitor Drug: Palbociclib CDK 4/6 Inhibitor Drug: Fulvestrant Endocrine Therapy Drug: Letrozole Endorcine Therapy Drug: Anastrozole Endocrine Therapy Drug: Exemestane Endocrine Therapy
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	Drug: Camizestrant Camizestrant (AZD9833) is an orally bioavailable, next generation SERD with non-clinical and clinical activity in both ESR1 mutant and wild type settings . Drug: Abemaciclib CDK4/6 Inhibitor Drug: Ribociclib CDK4/6 Inhibitor Drug: Palbociclib CDK 4/6 Inhibitor

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]