Clinical trial NCT06380751: 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
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Advanced Breast Cancer
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-04-24
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility 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:

  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.

Primary outcomes:
measure: Progression-Free Survival
timeFrame: Up to approximately 59 months
Secondary outcomes:
measure: Overall Survival
timeFrame: Up to approximately 88 months
measure: Progression Free Survival 2
timeFrame: Up to approximately 59 months
measure: Time to chemotherapy
timeFrame: Up to approximately 59 months
measure: Objective Response Rate
timeFrame: Up to approximately 59 months
measure: Duration of Response
timeFrame: Up to approximately 59 months
measure: Participant-reported tolerability
timeFrame: Up to approximately 59 months
measure: 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)
timeFrame: Up to approximately 59 months
measure: 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)
timeFrame: Up to approximately 59 months
measure: Plasma concentrations of saruparib (AZD5305)
timeFrame: Up to approximately 59 months
measure: Plasma concentrations of camizestrant
timeFrame: Up to approximately 59 months
measure: 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.
timeFrame: Up to approximately 59 months
Other outcomes:
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country: Portugal
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country: Turkey
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country: Turkey
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city: Istanbul
country: Turkey
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city: Kayseri
country: Turkey
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city: Çankaya
country: Turkey
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city: Cambridge
country: United Kingdom
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city: Guildford
country: United Kingdom
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city: London
country: United Kingdom
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city: Manchester
country: United Kingdom
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city: Oxford
country: United Kingdom
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city: Swansea
country: United Kingdom
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city: Taunton
country: United Kingdom
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city: Truro
country: United Kingdom
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Study officials:
References: