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)

AstraZeneca

Status and phase

Enrolling

Phase 3

Conditions

Advanced Breast Cancer

Treatments

Drug: Exemestane

Drug: Ribociclib

Drug: Anastrozole

Drug: Fulvestrant

Drug: Saruparib (AZD5305)

Drug: Camizestrant

Drug: Letrozole

Drug: Palbociclib

Drug: Abemaciclib

Study type

Interventional

Funder types

Industry

Identifiers

NCT06380751

D9722C00001

Details and patient eligibility

About

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

Full description

Approximately 2,620 participants will be screened to achieve approximately 500 participants randomised to study intervention.

Participants will be randomised in a 2:2:1 ratio to one of the following intervention groups:

Arm 1: saruparib (AZD5305) plus camizestrant
Arm 2: Physician's choice CDK4/6i plus physician's choice ET
Arm 3: Physician's choice CDK4/6i plus camizestrant Treatment continues until BICR-confirmed disease progression, unacceptable toxicity occurs, or the participant withdraws consent.

Enrollment

500 estimated patients

Sex

All

Ages

18 to 130 years old

Volunteers

No Healthy Volunteers

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:
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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

500 participants in 3 patient groups

Arm 1: saruparib (AZD5305) plus camizestrant

Experimental group

Description:

participants will receive saruparib (AZD5305) orally and camizestrant orally

Treatment:

Drug: Camizestrant

Drug: Saruparib (AZD5305)

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

Active Comparator group

Description:

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

Treatment:

Drug: Abemaciclib

Drug: Palbociclib

Drug: Letrozole

Drug: Anastrozole

Drug: Fulvestrant

Drug: Ribociclib

Drug: Exemestane

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

Experimental group

Description:

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