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

Advanced Breast Cancer Clinical Trial

— EvoPAR-BR01  

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06380751
• Other study ID #: D9722C00001
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 18, 2024
• Est. completion date: July 18, 2030

Study information

• Verified date: April 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 500
• Est. completion date: July 18, 2030
• Est. primary completion date: March 30, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Saruparib (AZD5305)
Saruparib (AZD5305) is a potent and selective inhibitor of PARP1, with minimal effect on PARP2.
• Camizestrant
Camizestrant (AZD9833) is an orally bioavailable, next generation SERD with non-clinical and clinical activity in both ESR1 mutant and wild type settings .
• Abemaciclib
CDK4/6 Inhibitor
• Ribociclib
CDK4/6 Inhibitor
• Palbociclib
CDK 4/6 Inhibitor
• Fulvestrant
Endocrine Therapy
• Letrozole
Endorcine Therapy
• Anastrozole
Endocrine Therapy
• Exemestane
Endocrine Therapy

Locations

Country	Name	City	State
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montréal	Quebec
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	Toronto
Canada	Research Site	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival	OS is defined as the time from randomisation until the date of death due to any cause.	Up to approximately 88 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Plasma concentrations of saruparib (AZD5305)		Up to approximately 59 months
Secondary	Plasma concentrations of camizestrant		Up to approximately 59 months
Secondary	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