Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292) (CAPItello-292)

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ClinicalTrials.gov Identifier: NCT04862663

Recruitment Status : Recruiting

First Posted : April 28, 2021

Last Update Posted : May 10, 2024

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Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

March 17, 2021

First Posted Date ^ICMJE

April 28, 2021

Last Update Posted Date

May 10, 2024

Actual Study Start Date ^ICMJE

May 10, 2021

Estimated Primary Completion Date

November 1, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Phase Ib: 1. The number of participants with dose-limiting toxicity, as defined in the protocol. [ Time Frame: Within the first 28 day cycle. ]
Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria.
Phase Ib: 2. The number of participants with treatment-related adverse events. [ Time Frame: From baseline up to approximately 36 months. ]
Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.
Phase Ib: 3. The number of participants with treatment-related serious adverse events. [ Time Frame: From baseline up to approximately 36 months. ]
Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.
Phase III: 1. Progression Free Survival (PFS). [ Time Frame: Up to approximately 47 months. ]
Progression Free Survival (PFS) is defined as time from randomization until progression per RECIST v1.1. as assessed by BICR or death due to any cause. RECIST related endpoints such as PFS, ORR, DoR, CBR will be collected

Original Primary Outcome Measures ^ICMJE

Phase Ib: 1. The number of participants with dose-limiting toxicity, as defined in the protocol. [ Time Frame: Within the first 28 day cycle. ]
Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optimal therapeutic intervention, meets protocol-defined criteria.
Phase Ib: 2. The number of participants with treatment-related adverse events. [ Time Frame: From baseline up to approximately 24 months. ]
Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.
Phase Ib: 3. The number of participants with treatment-related serious adverse events. [ Time Frame: From baseline up to approximately 24 months. ]
Data will include clinical observations, ECG parameters, clinical chemistry and haematology and vital signs assessed as the number of participants with treatment-related adverse events.
Phase III: 1. Progression Free Survival (PFS). [ Time Frame: Up to approximately 33 months. ]
Progression Free Survival (PFS) is defined as time from randomization until progression per RECIST v1.1. as assessed by the investigator or death due to any cause.

Change History

Current Secondary Outcome Measures ^ICMJE

Phase Ib: 1. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmax. [ Time Frame: Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days). ]
Maximum observed plasma (peak) drug concentration.
Phase Ib: 2. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-72h. [ Time Frame: Cycle 0 (Cycle 0 is 3 days). ]
Partial area under the plasma concentration-time curve from zero to 72 hours post-dose.
Phase Ib: 3. PK parameters for Palbociclib, Ribociclib, Abemaciclib: AUC0-24h. [ Time Frame: Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days). ]
Partial area under the plasma concentration-time curve from zero to 24 hours post-dose.
Phase Ib: 4. PK parameters for Palbociclib, Ribociclib, Abemaciclib: Cmin. [ Time Frame: Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 0 is 3 days and Cycle 1 is 28 days). ]
Minimum observed plasma drug concentration.
Phase Ib: 5. PK parameters for capivasertib: Cmax. [ Time Frame: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days). ]
Maximum observed plasma (peak) drug concentration.
Phase Ib: 6. PK parameters for capivasertib: AUC0-12h. [ Time Frame: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days). ]
Partial area under the plasma concentration-time curve from zero to 12 hours post-dose.
Phase Ib: 7. PK parameters for capivasertib: Cmin. [ Time Frame: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days). ]
Minimum observed plasma drug concentration.
Phase Ib: 8. Objective Response Rate (ORR). [ Time Frame: Up to approximately 36 months. ]
Objective Response Rate (ORR) is defined as the proportion of patients with measurable disease at baseline who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator at local site per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Phase Ib: 9. Clinical Benefit Rate (CBR) at 24 weeks. [ Time Frame: Up to approximately 36 months. ]
Clinical Benefit Rate (CBR) 24 weeks is defined as the percentage of patients who have a CR or PR or who have SD per RECIST v1.1 as assessed by the investigator at local site for at least 23 weeks after date of first dose.
Phase Ib: 10. Duration of Response (DoR). [ Time Frame: Up to approximately 36 months. ]
Duration of Response (DoR) will be defined as the time from the date of first documented confirmed response until date of documented progression per RECIST v1.1 as assessed by the investigator at local site or death due to any cause.
Phase Ib: 11. Progression Free Survival (PFS). [ Time Frame: Up to approximately 36 months. ]
Progression Free Survival (PFS) is defined as time from date of first dose until progression per RECIST v1.1. as assessed by the investigator at local site or death due to any cause.
Phase III: 1. Overall Survival (OS). [ Time Frame: Up to approximately 69 months. ]
Overall Survival (OS) - time from randomisation until the date of death due to any cause.
Phase III: 2. Objective Response Rate (ORR). [ Time Frame: Up to approximately 47 months. ]
Objective Response Rate (ORR) - the proportion of patients who have a complete or partial response), as determined by BICR per RECIST v1.1.
Phase III: 3. Duration of Response (DoR). [ Time Frame: Up to approximately 47 months. ]
Duration of Response (DoR) - the time from the date of first documented response until the date of progression per RECIST v1.1 as assessed by BICR, or death due to any cause.
Phase III: 4. Clinical Benefit Rate (CBR) at 24 weeks. [ Time Frame: Up to approximately 47 months. ]
Clinical Benefit Rate (CBR) at 24 weeks-the % of patients who have a CR or PR or who have SD per RECIST v1.1 as assessed by BICR for at least 23 weeks after randomisation.
Phase III: 5. Participant-reported physical functioning [ Time Frame: Up to approximately 69 months. ]
TTD of physical functioning as measured by the physical functioning subscale of the EORTC QLQ-C30.
Phase III: 6. participant-reported GHS/QoL in participants [ Time Frame: Up to approximately 69 months. ]
TTD of GHS/QoL as measured by the GHS/QoL subscale of the EORTC QLQ-C30.
Phase III: 7. Participant-reported overall side effect bother in participants in the capivasertib arm relative to control arm [ Time Frame: Up to approximately 69 months. ]
Proportion of participants experiencing different levels of overall treatment tolerability as measured by the Patient Global Impression-Treatment Tolerability (PGI-TT).
Phase III: 8. Plasma concentration of capivasertib pre- and post-dose. [ Time Frame: Up to approximately 69 months. ]
Plasma concentration of capivasertib pre-, and post-dose.
Phase III: 9. The number of participants with adverse events. [ Time Frame: Up to approximately 69 months. ]
Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with adverse events.
Phase III: 10. The number of participants with serious adverse events. [ Time Frame: Up to approximately 69 months. ]
Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with serious adverse events.

Original Secondary Outcome Measures ^ICMJE

Phase Ib: 1. PK parameters for palbociclib: Cmax. [ Time Frame: Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days). ]
Maximum observed plasma (peak) drug concentration.
Phase Ib: 2. PK parameters for palbociclib: AUC0-72h. [ Time Frame: Cycle 0 (Cycle 0 is 3 days). ]
Partial area under the plasma concentration-time curve from zero to 72 hours post-dose.
Phase Ib: 3. PK parameters for palbociclib: AUC0-24h. [ Time Frame: Cycle 0 (Cycle 0 is 3 days), Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 1 is 28 days). ]
Partial area under the plasma concentration-time curve from zero to 24 hours post-dose.
Phase Ib: 4. PK parameters for palbociclib: Cmin. [ Time Frame: Cycle 1 Day 11 and Cycle 1 Day 14 (Cycle 0 is 3 days and Cycle 1 is 28 days). ]
Minimum observed plasma drug concentration.
Phase Ib: 5. PK parameters for capivasertib: Cmax. [ Time Frame: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days). ]
Maximum observed plasma (peak) drug concentration.
Phase Ib: 6. PK parameters for capivasertib: AUC0-12h. [ Time Frame: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days). ]
Partial area under the plasma concentration-time curve from zero to 12 hours post-dose.
Phase Ib: 7. PK parameters for capivasertib: Cmin. [ Time Frame: Cycle 1 Day 11 (Cycle 0 is 3 days and Cycle 1 is 28 days). ]
Minimum observed plasma drug concentration.
Phase Ib: 8. Objective Response Rate (ORR). [ Time Frame: Up to approximately 24 months. ]
Objective Response Rate (ORR) is defined as the proportion of patients with measurable disease at baseline who have a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator at local site per Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
Phase Ib: 9. Clinical Benefit Rate (CBR) at 24 weeks. [ Time Frame: Up to approximately 24 months. ]
Clinical Benefit Rate (CBR) 24 weeks is defined as the percentage of patients who have a CR or PR or who have SD per RECIST v1.1 as assessed by the investigator at local site for at least 23 weeks after date of first dose.
Phase Ib: 10. Duration of Response (DoR). [ Time Frame: Up to approximately 24 months. ]
Duration of Response (DoR) will be defined as the time from the date of first documented confirmed response until date of documented progression per RECIST v1.1 as assessed by the investigator at local site or death due to any cause.
Phase Ib: 11. Progression Free Survival (PFS). [ Time Frame: Up to approximately 24 months. ]
Progression Free Survival (PFS) is defined as time from date of first dose until progression per RECIST v1.1. as assessed by the investigator at local site or death due to any cause.
Phase III: 1. Overall Survival (OS). [ Time Frame: Up to approximately 60 months. ]
Overall Survival (OS) - time from randomisation until the date of death due to any cause.
Phase III: 2. Progression Free Survival (PFS) in PIK3CA/ AKT1/ PTEN-altered population. [ Time Frame: Up to approximately 33 months. ]
Progression Free Survival (PFS) - time from randomisation until progression per RECIST v 1.1 as assessed by the PI or death due to any cause.
Phase III: 3. Progression Free Survival 2 (PFS2). [ Time Frame: Up to approximately 60 months. ]
Progression Free Survival (PFS2) - time from randomisation to the earliest of the progression event, subsequent to first therapy or death.
Phase III: 4. Objective Response Rate (ORR). [ Time Frame: Up to approximately 33 months. ]
Objective Response Rate (ORR) - the proportion of patients who have a complete or partial response.
Phase III: 5. Duration of Response (DoR). [ Time Frame: Up to approximately 33 months. ]
Duration of Response (DoR) - the time from the date of first documented response until the date of progression or death.
Phase III: 6. Clinical Benefit Rate (CBR) at 24 weeks. [ Time Frame: Up to approximately 33 months. ]
Clinical Benefit Rate (CBR) at 24 weeks-the % of patients who have a CR or PR or who have SD for at least 23 weeks after randomization.
Phase III: 7. EORTC QLQ-30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items). [ Time Frame: Up to approximately 60 months. ]
5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), and global health status/QoL scale, along with 5 individual item symptom scores (appetite loss, dyspnoea, insomnia, constipation, and diarrhoea. The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual (Fayers et al. 2001). Higher scores on the global measure of health status and functional scales indicate better health status/function, but higher scores on symptom scales/scores represent greater symptom severity.
Phase III: 8. 1.EORTC QLQ BR45 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire breast cancer specific module). [ Time Frame: Up to approximately 60 months. ]
The self-administered instrument includes 23-items and yields 5 multi-item scores (body image, sexual functioning, arm symptoms, breast symptoms, and systemic therapy side effects). Additional items yield two multi-item scales: a target symptom scale with three subscales (endocrine therapy, endocrine sexual and skin/mucosa) and a satisfaction scale. In addition, 3 single items are included that assess sexual enjoyment, future perspective and being upset by hair loss. Items are scored on a 4-point verbal rating scale: "Not at All," "A Little," "Quite a Bit," and "Very Much". Scores are transformed to a 0 to 100 scale, where higher scores indicate better functioning, better HRQoL, or greater level of symptoms.
Phase III: 9. Time to definitive deterioration of the ECOG (Eastern Cooperative Oncology Group) performance status. [ Time Frame: Up to approximately 60 months. ]
Time from randomisation to the earlier of the date of the first definitive deterioration or death due to any cause. Deterioration is defined as a 1-point decrease in ECOG score from baseline.
Phase III: 10. Plasma concentration of capivasertib pre- and post-dose. [ Time Frame: Up to approximately 60 months. ]
Plasma concentration of capivasertib pre-, and post-dose.
Phase III: 11. The number of participants with adverse events. [ Time Frame: Up to approximately 60 months. ]
Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with adverse events.
Phase III: 12. The number of participants with serious adverse events. [ Time Frame: Up to approximately 60 months. ]
Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with serious adverse events.

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

Capivasertib + CDK4/6i + Fulvestrant for Advanced/Metastatic HR+/HER2- Breast Cancer (CAPItello-292)

Official Title ^ICMJE

A Phase Ib/III, Open-label, Randomised Study of Capivasertib Plus CDK4/6 Inhibitors and Fulvestrant Versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292)

Brief Summary

A Phase Ib/III Open-label, Randomised Study of Capivasertib plus CDK4/6 Inhibitors and Fulvestrant versus CDK4/6 Inhibitors and Fulvestrant in Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced, Unresectable or Metastatic Breast Cancer (CAPItello-292)

Detailed Description

This Phase Ib/III study (CAPItello-292) aims to evaluate the efficacy, safety and the degree of added benefit of capivasertib combined with CDK4/6i and fulvestrant in participants with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer. Although the dosing regimens of capivasertib + fulvestrant and of CDK4/6i + fulvestrant are established separately, the dose and schedule for the triplet combinations (capivasertib + CDK4/6i + fulvestrant) need to be confirmed. Therefore, the initial dose finding Phase Ib part of the study will determine the recommended Phase III doses (RP3D) of the triplet combinations. The Phase III part of the study will evaluate the efficacy, safety and the degree of added benefit of the triplet combinations of capivasertib and fulvestrant with investigator's choice of CDK4/6i (either palbociclib or ribociclib at safe and tolerable doses, once identified) in comparison with a control arm (fulvestrant + investigator's choice of CDK4/6i [palbociclib or ribociclib]) in a ER+ HER2- maC high risk population that did not receive prior endocrine therapy in the advanced setting.

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Phase Ib: Open, Parallel groups allowed, recruiting up to approx. 222 participants.

Phase III: open-label, randomised, recruiting approx. 794 participants.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition ^ICMJE

Locally Advanced (Inoperable) or Metastatic Breast Cancer

Intervention ^ICMJE

Drug: Capivasertib
Phase Ib: Capivasertib 320 mg/ 400 mg administered PO BD 4 days on /3 days off per week for 4 weeks (28 days cycle) Phase III: : Capivasertib, administered PO BD 4 days on / 3 days off per week for 4 weeks (28 days cycle) at the dose confirmed in the phase Ib portion
Drug: Fulvestrant
Phase Ib and Phase III: 500 mg (2 injections of 250 mg) on Day 1 of Weeks 1 and 3 of Cycle 1, and then on Day 1, Week 1 of each cycle thereafter
Drug: Palbociclib
Phase Ib: 100 mg/ 125 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose of 125 mg.
Drug: Ribociclib
Phase Ib: 200 mg/ 400 mg/ 600 mg. Once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete 28-day cycle Phase III: Administered once daily for 21 days of 28-day cycle, at the dose confirmed in the phase 1b portion.
Drug: Abemaciclib
Phase Ib: 50 mg/ 100 mg/ 150 mg. Twice daily for 28 consecutive days to comprise a complete 28-day cycle

Study Arms ^ICMJE

Experimental: Capivasertib Plus Palbociclib and Fulvestrant
Capivasertib Plus Palbociclib and Fulvestrant (Ph 1b)
Interventions:
- Drug: Capivasertib
- Drug: Fulvestrant
- Drug: Palbociclib
Experimental: Capivasertib Plus Ribociclib and Fulvestrant
Capivasertib Plus Ribociclib and Fulvestrant (Ph 1b)

Intervention: Drug: Ribociclib
Experimental: Capivasertib Plus Abemaciclib and Fulvestrant
Capivasertib Plus Abemaciclib and Fulvestrant (Ph 1b)

Intervention: Drug: Abemaciclib
Experimental: Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib)
Capivasertib Plus Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III)

Intervention: Drug: Capivasertib
Active Comparator: Fulvestrant and Investigator's choice of CDK4/6i (palbociclib or ribociclib)
Fulvestrant and investigator's choice of CDK4/6i (palbociclib or ribociclib) (Ph III)

Intervention: Drug: Fulvestrant

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

895

Original Estimated Enrollment ^ICMJE

700

Estimated Study Completion Date ^ICMJE

August 14, 2029

Estimated Primary Completion Date

November 1, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Key inclusion criteria for both phases:

Adult females (pre-/peri-/ and post-menopausal), and adult males.
Histologically confirmed HR+/ HER2- breast cancer determined from the most recent tumour sample (primary or metastatic) per the American Society of Clinical Oncology and College of American Pathologists guideline. To fulfil the requirement of HR+ disease, a breast cancer must express ER with or without co-expression of progesterone receptor.
Eligible for fulvestrant therapy and at least one of the following: palbociclib, ribociclib, or abemaciclib, as per local investigator assessment. Previous tolerance to specific CDK4/6 inhibitors and dose levels required.
Adequate organ and bone marrow functions.
Consent to provide a mandatory FFPE tumour sample.

Key inclusion criteria only for phase III:

Previous treatment with an ET (tamoxifen, AI, or oral SERD) as a single agent or in combination, with radiological evidence of breast cancer recurrence or progression while on, or within 12 months of, completing a (neo)adjuvant ET regimen.
Provision of mandatory blood samples at screening for central testing using an investigational ctDNA test to be stratified based on PIK3CA/AKT1/PTEN status.
Be eligible for fulvestrant and at least one out of palbociclib or ribociclib (depending on the available CDK4/6i options at time of enrolment), as per local investigator assessment.
Have measurable lesion(s) according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) or, in the absence of measurable disease, lytic or mixed bone lesions that can be assessed by computed tomography (CT) or magnetic resonance imaging (MRI).

Key exclusion criteria for both phases:

History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence.
Radiotherapy within 2 weeks prior to study treatment initiation.
Major surgery or significant traumatic injury within 4 weeks of the first dose of study treatment.
Persistent toxicities (CTCAE Grade >1) caused by previous anticancer therapy, excluding alopecia. Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss or peripheral sensory neuropathy) after consultation with the AstraZeneca study physician.
Spinal cord compression, brain metastases or leptomeningeal metastases unless these lesions are definitively treated (eg. radiotherapy, surgery) and clinically stable off steroids for management of symptoms for at least 4 weeks prior to study treatment initiation.
Any of the following cardiac criteria at screening:

(a). Mean resting corrected QT interval (QTcF): (i) Participants to be treated with palbociclib:: QTcF ≥ 470 ms obtained from the average of 3 consecutive (triplicate) ECGs (ii) Participants to be treated with ribociclib: QTcF ≥ 450 ms obtained from the average of 3 consecutive (triplicate) ECGs (iii) Participants to be treated with abemaciclib (Phase Ib only): QTcF ≥ 470 ms obtained from the average of 3 consecutive (triplicate) ECGs (b). Any clinically important abnormalities in cardiac rhythm, conduction or morphology of resting ECG (eg, complete left bundle branch block, third-degree heart block) (c). Any factors that increase the risk of QTc prolongation or risk of arrhythmic events (d). Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, unstable angina pectoris, congestive heart failure New York Heart Association (NYHA) grade ≥ 2 (e). Uncontrolled hypotension (f) uncontrolled hypertension (g). Cardiac ejection fraction outside institutional range of normal or < 50% (whichever is higher)
uncontrolled or high grade or symptomatic arrhythmia and atrial fibrillation
Any of these clinically significant abnormalities of glucose metabolism at screening:
1. . diabetes mellitus type I or type II requiring insulin treatment
2. . Glycated haemoglobin (HbA1c) ≥ 8.0% (63.9 mmol/mol)
Previous allogeneic bone marrow transplant or solid organ transplant.

Key exclusion criteria for the phase III only:

Any prior treatment with, AKT, PI3K or mTOR inhibitors.
Prior treatment with CDK4/6 inhibitors in the metastatic setting (prior CDK4/6 inhibitors permitted in the adjuvant setting provided there was a CDK4/6i treatment free interval of at least 12 months).
More than 1 line of chemotherapy for metastatic disease

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 99 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact: AstraZeneca Clinical Study Information Center	1-877-240-9479	information.center@astrazeneca.com
Contact: AZ Breast Cancer Study Navigators	+1-877-400-4656	AstraZeneca@CareboxHealth.com

Listed Location Countries ^ICMJE

Argentina, Australia, Belgium, Brazil, Canada, China, Denmark, France, Germany, India, Italy, Japan, Korea, Republic of, Malaysia, Poland, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States, Vietnam

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT04862663

Other Study ID Numbers ^ICMJE

D361DC00001
2020-004637-20 ( EudraCT Number )

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:	Yes
Plan Description:	Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Supporting Materials:	Study Protocol
Supporting Materials:	Statistical Analysis Plan (SAP)
Time Frame:	AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Access Criteria:	When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
URL:	https://astrazenecagroup-dt.pharmacm.com/DT/Home