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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

PHASE3RECRUITING

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.

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Study details:

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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2024-08-01

Primary completion: 2029-03-30

Study completion finish: 2030-10-18

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT06380751

Intervention or treatment

DRUG: Saruparib (AZD5305)

DRUG: Camizestrant

DRUG: Abemaciclib

DRUG: Ribociclib

DRUG: Palbociclib

DRUG: Fulvestrant

DRUG: Letrozole

DRUG: Anastrozole

DRUG: Exemestane

Conditions

• Advanced Breast Cancer

Condition: Advanced Breast Cancer
DRUG: Saruparib (AZD5305) and other drugs
Darlinghurst, Not Specified, Australia
Sponsor: AstraZeneca

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Closest Location:

Research Site

Research sites nearby

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Research Site
Darlinghurst, Not Specified, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
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.
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	DRUG: Abemaciclib CDK4/6 Inhibitor
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 .

What is the study measuring?

Primary outcome

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

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Overall Survival	OS is defined as the time from randomisation until the date of death due to any cause.	Up to approximately 88 months
Progression Free Survival 2	PFS2 is defined as the time from randomisation to the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death.	Up to approximately 59 months
Time to chemotherapy	Time to chemotherapy is defined as time from randomisation until the start date of the first subsequent chemotherapy treatment after discontinuation of randomised treatment (censoring participants who died prior to initiation of chemotherapy).	Up to approximately 59 months
Objective Response Rate	ORR is defined as the proportion of participants who have a complete or parial response, as determined by BICR per RECIST v1.1.	Up to approximately 59 months
Duration of Response	DoR is defined as the time from the date of first documented response until date of documented progression per RECIST v1.1 as assessed by BICR, or death due to any cause.	Up to approximately 59 months
Participant-reported tolerability	Proportion of all dosed participants reporting different levels of severity of diarrhoea as measured by the diarrhoea single item (EORTC IL237/IL239/IL240) and different levels of severity of abdominal pain as measured by the abdominal pain single item (EORTC IL237/IL239/IL240).	Up to approximately 59 months
Time to deterioration in patient-reported global health status/QoL as measured by the global health status/QoL scale within the The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)	This scale includes 2 items asking participants to report overall health and overall quality of life in the past week. Both items are measured on a 6-point verbal rating scale ranging from Very Poor to Excellent. Single item scores are averaged to calculate a subscale score that is transformed to range from 0 to 100, where higher scores indicate better global health status/QoL.	Up to approximately 59 months
Change from baseline in patient-reported global health status/QoL as measured by the global health status/QoL scale within the The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)	This scale includes 2 items asking participants to report overall health and overall quality of life in the past week. Both items are measured on a 6-point verbal rating scale ranging from Very Poor to Excellent. Single item scores are averaged to calculate a subscale score that is transformed to range from 0 to 100, where higher scores indicate better global health status/QoL.	Up to approximately 59 months
Plasma concentrations of saruparib (AZD5305)	Not Specified	Up to approximately 59 months
Plasma concentrations of camizestrant	Not Specified	Up to approximately 59 months
Samples will be used to develop companion diagnostics by analyzing their performance characteristics and calculate their consistency with clinical trial assays used for enrolment onto the study.	Samples will be tested by a CDx to confirm BRCA1/2 and PALB2 gene mutation status	Up to approximately 59 months

Frequently Asked Questions

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References

Clinical Trials Gov: 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