CTRI/2025/03/082512 [Registered on: 18/03/2025] Trial Registered Prospectively
Last Modified On:
27/02/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
Study of Saruparib (AZD5305) Plus Camizestrant for treatment of Patients with BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor-Positive, HER2 Negative Advanced Breast Cancer
Scientific Title of Study
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 Plus, 2Plus ISH non amplified) Advanced Breast Cancer (EvoPAR-Breast01)
Trial Acronym
EvoPAR-Breast01
Secondary IDs if Any
Secondary ID
Identifier
D9722C00001 Version no.2.0 dated 30 Jan 2024
Protocol Number
NCT06380751
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Site Management & Monitoring India
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
Bangalore KARNATAKA 560045 India
Phone
9845079472
Fax
Email
sandeep.av@astrazeneca.com
Details of Contact Person Scientific Query
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Site Management & Monitoring India
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
KARNATAKA 560045 India
Phone
9845079472
Fax
Email
sandeep.av@astrazeneca.com
Details of Contact Person Public Query
Name
Mr Sandeep AV
Designation
Senior Director, Oncology Country Head, Site Management & Monitoring India
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
KARNATAKA 560045 India
Phone
9845079472
Fax
Email
sandeep.av@astrazeneca.com
Source of Monetary or Material Support
AstraZeneca AB
151 85 Sodertalje, Sweden
Primary Sponsor
Name
AstraZeneca AB
Address
151 85 Sodertalje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Ltd
Block N1, 12th Floor, Manyata Embassy Business Park
Rachenahalli, Outer Ring Road, Bangalore – 560045, India
Countries of Recruitment
Argentina Australia Austria Brazil Bulgaria Chile China Czech Republic France Germany Hungary India Israel Italy Japan Malaysia Peru Poland Portugal Republic of Korea Spain Taiwan Thailand Turkey United Kingdom United States of America
Sites of Study
No of Sites = 10
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Atul Batra
All India Institute of Medical Sciences (AIIMS)
Department of Medical Oncology, Room No.216, Dr. B.R.A.-IRCH, Ansari Nagar, New Delhi-11002 New Delhi DELHI
011 26588500
batraatul85@gmail.com
Dr Srinivas K G
Bharath Hospital and Institute of Oncology
Department of Medical Oncology
No. 438, Outer Ring Road, Hebbal Industrial Area, Lakshmikanth Nagar, Mysore - 570 017, Karnataka
Mysore KARNATAKA
9663121728
drsrinivaskg2020@gmail.com
Dr Mukesh Chaudhari
HCG Manavata Cancer Centre
Department of Medical Oncology,
Behind Shivang Auto, Mumbai Naka, Nashik, 422002,
Nashik MAHARASHTRA
9096920416
drmukesh@mcrinasik.com
Dr Saurabh Prasad
KIMS-Kingsway Hospitals
Department of Medical Oncology,
44, Parwana Bhavan, Kingsway Road, Nagpur, Maharashtra-440001
Nagpur MAHARASHTRA
7066580511
drsaurabhprasad@gmail.com
Dr Vijay Patil
PD Hinduja Hospital and Medical Research Centre
Department of Medical Oncology
724, Marvela Building, 11th Road, Khar, Mumbai – 400052
Mumbai MAHARASHTRA
9136129135
vijaypgi@gmail.com
Dr Dinesh Doval
Rajiv Gandhi Cancer Institute and Research Centre
Department of Medical Oncology
Sir Chotu Ram Marg, Sector – 5, Rohini, New Delhi – 110085
New Delhi DELHI
9822012427
dcdoval@gmail.com
Dr Rona Joseph
Regional Cancer Centre, Medical College
Department of Medical Oncology
Kumarapuram Rd, Medical College Campus, Chalakkuzhi, Thiruvananthapuram, Kerala 695011
Thiruvananthapuram KERALA
8281468929
ronsjsph@gmail.com
Dr Ankit Patel
Sunshine Global Hospital
Department of Medical Oncology
Piplod, Beside Big Bazar, Gaurav Path, Dumas road, Surat-395007
Surat GUJARAT
9825404202
drankitoncologist@gmail.com
Dr Somnath Roy
Tata Medical Center
Department of Medical Oncology
14,Major Arterial Road (EW),New Town Rajarhat, Kolkata, West Bengal,
700160, India
Kolkata WEST BENGAL
9051732283
somnath.roy1@tmckolkata.com
Dr Prabhat Bhargava
Tata Memorial Hospital
Homi Bhabha Block Building, Department of Medical Oncology
11th Floor, 1102, Dr Ernest Borges Marg, Parel, Mumbai 400012
Mumbai MAHARASHTRA
7276174221
bhargava611@gmail.com
Details of Ethics Committee
No of Ethics Committees= 10
Name of Committee
Approval Status
Human Ethics Committee RCC Regional Cancer Centre
Submittted/Under Review
Institutional Ethics Committee Sunshine Global Hospital,
Approved
Institutional Ethics Committee, All India Institute of Medical Sciences
Submittted/Under Review
Institutional Ethics Committee, Bharath Hospital and Institute of Oncology
Submittted/Under Review
Institutional Ethics Committee, PD Hinduja Hospital and Medical Research Centre,
Submittted/Under Review
Institutional Ethics Committee-II, Tata Memorial Hospital,
Submittted/Under Review
Institutional Review Board Rajiv Gandhi Cancer Institute and Research Centre
Approved
Institutional Review Board, Tata Medical Center
Submittted/Under Review
Kingsway Hospitals Ethics Committee
Submittted/Under Review
Manavata Clinical Research Institute Ethics Committee
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C501||Malignant neoplasm of central portion of breast,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Physician’s choice CDK4/6i plus ET or plus camizestrant
Physician’s Choice CDK4/6i:
150 mg abemaciclib orally twice daily, or
600 mg ribociclib orally daily for 21 days followed by 7 days off during a 28 day cycle, or
125 mg palbociclib orally daily for 21 days followed by 7 days off during a 28 day cycle.
Physician’s Choice ET:
500 mg fulvestrant intramuscular
One of the following AIs:
2.5 mg letrozole orally daily, or
1 mg anastrozole orally daily, or
25 mg exemestane orally daily
Intervention
Saruparib (AZD5305) plus camizestrant
Saruparib (AZD5305) plus camizestrant
– route of administration is oral
Physician’s choice CDK4/6i plus ET or plus camizestrant
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age and Sex
1 Participants must be 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of signing the ICF.
2 Adult females, pre/peri-menopausal and/or post-menopausal, and adult males
(a) Pre/peri-menopausal women (ie, those who do not meet the criteria for post menopausal defined below) can be enrolled if amenable to treatment with an LHRH agonist. Participants are to have commenced concomitant treatment with an LHRH agonist prior to or on Cycle 1 Day 1 and must be willing to continue on it for the duration of the study.
(b) Post-menopausal women are defined as:
(i) aged 60 years of age, OR
(ii) aged 60 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments/chemotherapy/ovarian suppression/tamoxifen or similar. These participants should also have serum estradiol and FSH levels confirmed as being within the standard laboratory reference range for post-menopausal females, OR
(iii) documented bilateral oophorectomy.
(c) Male participants can be enrolled if amenable to be treated with an LHRH agonist unless the participants have clear orchiectomy medical history. Participants are to have commenced concomitant treatment with an LHRH agonist prior to or on Cycle 1 Day 1 and must be willing to continue on it for the duration of the study.
Type of Participant and Disease Characteristics
1 Histologically or cytologically documented diagnosis of HR-positive, HER2-negative breast cancer based on local laboratory results.
( ) Documentation of ER 1parcentege positive stained cells, assessed on most recent tumour biopsy utilising an assay consistent with ASCO CAP 2020 guidelines (Allison et al 2020). Refer to Appendix K, if only Allred or H-score is available.
(a) Documented HER2-negative tumour based on local testing on most recent tumour biopsy: HER2-negative tumour is determined as IHC score 0/1+ or negative by in situ hybridisation (fluorescence in situ hybridization [FISH], chromogenic in situ hybridization [CISH], silver in situ hybridization [SISH], dual colour in situ hybridization [DISH]), defined as a HER2/centromere 17 (CEP17) ratio 2 or for single probe assessment a HER2 copy number 4, consistent with ASCO CAP 2018 guidelines (Wolff et al 2018).
4 Advanced breast cancer with either locally advanced disease not amenable to curative treatment or metastatic disease. Participants must have at least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT (MRI where CT is contraindicated) and is suitable for repeated assessment as per RECIST v1.1.
5 ECOG performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline at screening and prior to randomisation.
6 Minimum life expectancy of 12 weeks.
7 FFPE tumour tissue from each participant is required, as per the Central Laboratory Services Manual. Written confirmation of the availability of an archival FFPE tumour sample is to be provided, meeting the study requirement for randomisation.
8 Participants must have:
( ) Documented germline tumour loss of function mutation in BRCA1, BRCA2, or PALB2 by local testing performed either in a CLIA/CAP-certified laboratory (United States), in a locally accredited laboratory (outside United States), or by a qualified laboratory accepted by the sponsor (for China only). These participants can be randomised into the study based on the known germline status, OR
(a) tumour loss of function mutation in BRCA1, BRCA2, or PALB2 determined by central tissue testing.
9 Adequate organ and marrow function, as follows:
( ) Haemoglobin 10.0 g/dL with no blood transfusion in the 14 days prior to randomisation
(a) Absolute neutrophil count 1.5 109/L with no growth factor support in the 28 days prior to randomisation
(b) Platelet count 100 into 109/L
(c) Serum albumin 3.0 g/dL
(d) INR 1.5. Participants receiving oral anticoagulants may be enrolled with an INR 2. Participants with clinical causes of INR increase such as bleeding disorders, impaired hepatic synthesis should be excluded.
Reproduction
10 Women who are not post-menopausal or have not undergone hysterectomy must have documented negative pregnancy test within 28 days prior to randomisation (post menopausal is defined in Inclusion Criterion 2.)
11 Female participants of child-bearing potential:
( ) Must have a negative pregnancy test result at screening and prior to each cycle of study treatment.
(a) If sexually active with a non-sterilised male partner, must use at least one highly effective method of birth control plus a barrier method (eg, condom with spermicide in accordance with local guidelines) from signing of ICF to approximately 6 months after the last dose of study treatment.
The use of hormonal contraceptive methods is not allowed. (See Appendix G 1 for examples of effective methods of birth control for females)
(b) Must not breastfeed and must not donate or retrieve ova for their own use from screening to approximately 6 months after the last dose of study treatment.
12 Male participants:
( ) Must use a condom (with spermicide [in accordance with local guidelines]) from screening to approximately 6 months after the last dose of study treatment with all sexual partners. Female partners of male participants who are of child-bearing potential should use a highly effective method of contraception throughout this period. (See Appendix G 2 for examples of effective methods of birth control for males).
(a) Must refrain from fathering a child or donate sperm during the study and for approximately 6 months after the last dose of study treatment.
Informed Consent
13 Capable of giving signed informed consent as described in Appendix A 3 which includes compliance with the requirements and restrictions listed in the ICF and in this CSP.
14 Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics research that supports the Genomics Initiative (see Appendix D).
ExclusionCriteria
Details
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1 Participants with history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). Specific screening for MDS/AML is not required.
2 Participants with any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy).
4 As judged by the investigator, any evidence of severe or uncontrolled systemic diseases or active uncontrolled infections, including but not limited to, uncontrolled major seizure disorder and active bleeding diseases, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on HRCT scan, history of allogenic organ transplant, which, in the investigator’s opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol.
8 Spinal cord compression, brain metastases, carcinomatous meningitis, or leptomeningeal disease unless definitively treated with local therapy, asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of brain radiotherapy and study enrolment.
Medical Conditions – Infections
9 Evidence of active and uncontrolled hepatitis B and/or hepatitis C. Screening for hepatitis B and hepatitis C is not required. Participants previously exposed to hepatitis B or hepatitis C are eligible if they meet one of the following criteria:
(e) Are negative for HBsAg and anti-HBc, or
(f) Are HbsAgPlus and anti-HbcPlus (chronic hepatitis B), and meet conditions i to iii below:
(i) HBV DNA viral load 2000 IU/L.
(ii) Have normal aminotransferase values, or, if liver metastases are present, abnormal aminotransferase, with a result of AST/ALT 3 into ULN, which are not attributable to HBV infection.
(iii) Start antiviral treatment at least 2 weeks prior to the first dose of study treatment and maintain antiviral treatment during the interventional period. For permitted concomitant therapies, refer to Appendix I.
(g) Are anti-HBc positive, HBs-Ag negative, and have HBV DNA 2000 IU/L.
(h) Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
NOTE: Inclusion of this group of participants should be carefully considered if participant has no access to hepatology service and/or is currently in need of antiviral treatments.
Medical Conditions - Cardiac
12 On screening, inability to determine the QTcF interval on the ECG (ie, unreadable or not interpretable).
13 Mean resting corrected QT interval (QTcF) 470 ms obtained from triplicate ECGs performed at screening and averaged, recorded 5 minutes apart, unless participants plan to be allocated to ribociclib, in which case QTcF 450 ms is an exclusion criterion (using Fridericia’s correction).
14 Resting heart rate 55 bpm for participants who are either taking heart rate reducing concomitant medications; or that have a history of stroke, or uncontrolled coronary heart disease, or dysrhythmia. Repeat measurements are permitted during the screening period.
15 Any factors that increase the risk of QTc prolongation or the risk of arrhythmic events such as symptomatic heart failure, congenital long QT syndrome, immediate family history of long QT syndrome, unexplained sudden cardiac death under 40 years of age or any concomitant medication known to prolong the QT interval (please refer to Appendix I 1.1), hypertrophic cardiomyopathy, clinically significant stenotic valve disease, clinically significant hypokalaemia, hyperkalaemia, hypo- and hyper-magnesaemia, hypo-and hyper-calcaemia. Correction of electrolyte abnormalities to within normal ranges can be performed during screening.
16 Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, eg, third degree heart block.
17 Left ventricular ejection fraction 50parcentege as measured by echocardiogram or MUGA at screening (or based on assessment performed within 4 months prior to randomisation) with congestive heart failure NYHA Grade 2.
18 Uncontrolled hypertension. Hypertensive participants may be eligible, but blood pressure must be adequately controlled at baseline. Participants may be rescreened regarding the blood pressure requirement.
19 Acute coronary syndrome /acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention or coronary artery bypass grafting, angioplasty or vascular stent within 6 months.
Prior/Concomitant Therapies that are not permitted. Please also refer to Table 6.
20 Concurrent exogenous reproductive hormone therapy (eg, birth control pills, hormone replacement therapy, Mirena intrauterine device, or megestrol acetate) or non-topical hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy). Please refer to Table 6 and Appendix G. Note: topical vaginal ET is permitted if all non-hormonal options have been exhausted.
21 Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study. Participants should have fully recovered from any clinically significant adverse events.
22 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. Participant should have fully recovered from any clinically significant adverse events.
23 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.
24 Prior treatment within 28 days with blood product support or growth factor support.
25 Any systemic concurrent anti-cancer treatment
26 Concomitant use of the following types of medications or herbal supplements within 21 days or at least 5 half-lives (whichever is longer) of randomisation:
(m) Strong and moderate CYP3A4 inducers/inhibitors
(n) Sensitive CYP2B6 substrates
(o) Substrates of CYP2C9 and/or CYP2C19 which have a narrow therapeutic index, eg, warfarin (and other coumarin-derived vitamin K antagonist anticoagulants) and phenytoin.
The above includes, but may not be limited to, the prohibited medications and herbal supplements listed in Section 6.9.1 and .
27 Concomitant use of drugs that are known to prolong QT and have a known risk of TdP as listed in
28 Systemic use of atropine.
29 The following exclusion criteria apply to treatments administered for early breast cancer:
(p) Disease progression 84 days following the last dose of neo-adjuvant or adjuvant chemotherapy
(q) Disease progression 1 year (365 days) from the last dose of treatment with a PARPi and/or platinum agent for early breast cancer
(r) Disease progression 1 year (365 days) from the last dose with a CDK4/6i in the adjuvant setting
(s) Disease progression 1 year (365 days) from the last dose of an oral SERD including camizestrant.
Other exclusion criteria:
30 Concurrent enrolment in another clinical study (unless the study is non-interventional, or the participant is in the follow-up period of an interventional study).
31 Participants with a known hypersensitivity to saruparib (AZD5305) or any of the investigator agents in the study or any of the excipients of these products.
32 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
33 Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
34 Previous randomisation in the present study.
35 For females only: Currently pregnant (confirmed with positive pregnancy test) or breast feeding, or who are planning to become pregnant.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To demonstrate the superiority of saruparib (AZD5305) + camizestrant relative to physician’s choice CDK4/6i + ET, by assessment of PFS.
To demonstrate the superiority of saruparib (AZD5305) + camizestrant relative to physician’s choice CDK4/6i + ET, by assessment of PFS. every 12 weeks
Secondary Outcome
Outcome
TimePoints
To demonstrate the superiority of saruparib (AZD5305) + camizestrant relative to physician’s choice CDK4/6i + ET by assessment of OS
OS is defined as the time from randomisation until the date of death due to any cause.
The analysis will include all randomised participants as randomised. All deaths will be included regardless of whether the participant withdraws from therapy or receives another anti cancer therapy.
The measure of interest is the hazard ratio of OS.
every 12 weeks
To evaluate the efficacy of saruparib (AZD5305) Plus camizestrant relative to physician’s choice CDK4 6i Plus ET by assessment of PFS2.
PFS2 is defined as the time from randomisation to the earliest of the progression event following the initial investigator-assessed progression, after first
To evaluate the efficacy of saruparib (AZD5305) + camizestrant relative to physician’s choice CDK4/6i + ET by assessment of 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).
To evaluate the efficacy of saruparib (AZD5305) + camizestrant relative to physician’s choice CDK4/6i + ET by assessment of ORR.
ORR is defined as the proportion of participants who have a CR or PR, as determined by BICR per RECIST v1.1.
To evaluate the efficacy of saruparib (AZD5305) + camizestrant relative to physician’s choice CDK4/6i + ET by assessment of DoR.
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.
To assess participant-reported tolerability of saruparib (AZD5305) + camizestrant relative to physician’s choice CDK4/6i + ET.
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).
To assess HRQoL while on saruparib (AZD5305) + camizestrant relative to physician’s choice CDK4/6i + ET.
Change from baseline and time to deterioration in scores on global health and global HRQoL items (EORTC IL237/IL238) for all randomised participants.
The analysis will include all randomised participants as randomised.
The measures of interest are the change from baseline and time to deterioration in scores on global health and global HRQoL (EORTC IL237/IL238).
To assess the PK of saruparib (AZD5305) and camizestrant in plasma and explore the relationship between the PK concentration or parameters and selected endpoints (which may include pharmacodynamic parameters, efficacy, and/or safety)
Plasma concentrations of saruparib (AZD5305) and camizestrant (parent and metabolite(s) if applicable), and plasma PK parameters, including but not limited to AUC, Cmax, and Tmax, as data allows.
To develop companion diagnostic testing for the detection of germline and/or somatic mutations in BRCA1/2 and PALB2 genes in participants with HR+, HER2- advanced breast cancer.
BRCA1/2 and PALB2 gene mutation status.
To describe the efficacy of saruparib (AZD5305) + camizestrant (Arm 1) relative to physician’s choice CDK4/6i + camizestrant (Arm 3).
Each of the efficacy endpoints and analyses described above for saruparib (AZD5305) camizestrant relative to physician’s choice CDK4/6i ET. No formal statistical hypothesis testing is planned.
To describe the efficacy of physician’s choice CDK4/6i + camizestrant (Arm 3) relative to physician’s choice CDK4/6i + ET (Arm 2).
Each of the efficacy endpoints and analyses described above for saruparib (AZD5305) camizestrant relative to physician’s choice CDK4/6i ET. No formal statistical hypothesis testing is planned.
To assess the safety and tolerability of saruparib (AZD5305) + camizestrant (Arm 1) relative to physician’s choice CDK4/6i + ET (Arm 2).
Safety and tolerability endpoints will include, but are not limited to: TEAEs, SAEs, AEs leading to dose modifications, changes from baseline in vital signs, clinical laboratory assessments, electrocardiograms, and physical examinations.
To describe the safety and tolerability of saruparib (AZD5305) + camizestrant (Arm 1) relative to physician’s choice CDK4/6i + camizestrant (Arm 3).
Each of the safety endpoints and analyses described above for saruparib (AZD5305) camizestrant relative to physician’s choice CDK4/6i ET
To describe the safety and tolerability of physician’s choice CDK4/6i + camizestrant (Arm 3) relative to physician’s choice CDK4/6i ET (Arm 2)
Each of the safety endpoints and analyses described above for saruparib (AZD5305) camizestrant relative to physician’s choice CDK4/6i ET.
Target Sample Size
Total Sample Size="500" Sample Size from India="30" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
01/04/2025
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
13/08/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="5" Months="0" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Overall Design
Participant Population:
The target population of interest in this study is patients with BRCA1, BRCA2, or PALB2 mutations and HR-positive, HER2-negative advanced breast cancer.Approximately 2,620 participants will be screened to achieve approximately 500 participants randomised to study intervention.
Study Arms and Duration:
The study will have 4 periods: biomarker testing, screening, treatment, and follow-up.
Prior to screening, the potential participants’ biomarker status must be assessed.
The screening period will commence once consent is obtained for the main study and will be up to 28 days.
The treatment period starts at first dose of study intervention and will continue until BICR-confirmed disease progression by RECIST v1.1, unacceptable toxicity occurs, or the participant withdraws consent.
The follow-up period will start after discontinuation of all study drugs.
Participants will be randomised in a 2:2:1 ratio to one of the following intervention groups:
Arm 1: saruparib (AZD5305) plus camizestrant: participants will receive saruparib (AZD5305) 60 mg orally once daily and camizestrant 75 mg orally once daily.
Arm 2: Physician’s choice CDK4/6i plus physician’s choice ET: dosing and agents are indicated below but should follow local guidelines.
Physician’s Choice CDK4/6i:
150 mg abemaciclib orally twice daily, or
600 mg ribociclib orally daily for 21 days followed by 7 days off during a 28day cycle, or
125 mg palbociclib orally daily for 21 days followed by 7 days off during a 28day cycle.
Physician’s Choice ET:
500 mg fulvestrant intramuscularly on days 1, 15, 29 and once monthly thereafter, or
One of the following AIs:
2.5 mg letrozole orally daily, or
1 mg anastrozole orally daily, or
25 mg exemestane orally daily.
Arm 3: Physician’s choice CDK4/6i plus camizestrant: participants will receive camizestrant 75 mg orally once daily. Dosing and agents for CDK4/6i treatment are indicated above but should follow local guidelines.