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Combination therapy for advanced breast cancer

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)

Phase 3 Interventional AstraZeneca · NCT04862663

This study is testing a new combination of treatments for people with advanced breast cancer to see if it works better than the standard care they currently receive.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment895 (estimated)
Ages18 Years to 99 Years
SexAll
SponsorAstraZeneca Industry-sponsored
Drugs / interventionschemotherapy
Locations283 sites (Tucson, Arizona and 282 other locations)
Trial IDNCT04862663 on ClinicalTrials.gov

What this trial studies

This Phase Ib/III study evaluates the effectiveness and safety of capivasertib combined with CDK4/6 inhibitors and fulvestrant in patients with locally advanced or metastatic HR+/HER2- breast cancer. The study consists of an initial Phase Ib dose-finding part to establish the recommended doses for the combination therapy, followed by a Phase III comparison of the triplet therapy against a control group receiving standard treatment. Participants will be monitored for efficacy and safety outcomes to determine the added benefit of the new combination regimen.

Who should consider this trial

Good fit: Ideal candidates include adult females and males with histologically confirmed HR+/HER2- breast cancer who are eligible for fulvestrant therapy and have not received prior endocrine therapy in the advanced setting.

Not a fit: Patients with HER2-positive breast cancer or those who have previously received endocrine therapy in the advanced setting may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective option for patients with advanced breast cancer, potentially improving survival rates and quality of life.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in treating HR+/HER2- breast cancer, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key inclusion criteria for both phases:

1. Adult females (pre-/peri-/ and post-menopausal), and adult males.
2. 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.
3. 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.
4. Adequate organ and bone marrow functions.
5. Consent to provide a mandatory FFPE tumour sample.

Key inclusion criteria only for phase III:

1. 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.
2. Provision of mandatory blood samples at screening for central testing using an investigational ctDNA test to be stratified based on PIK3CA/AKT1/PTEN status.
3. 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.
4. 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:

1. 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.
2. Radiotherapy within 2 weeks prior to study treatment initiation.
3. Major surgery or significant traumatic injury within 4 weeks of the first dose of study treatment.
4. 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.
5. 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.
6. 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)
7. uncontrolled or high grade or symptomatic arrhythmia and atrial fibrillation
8. 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)
9. Previous allogeneic bone marrow transplant or solid organ transplant.

Key exclusion criteria for the phase III only:

1. Any prior treatment with, AKT, PI3K or mTOR inhibitors.
2. 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).
3. More than 1 line of chemotherapy for metastatic disease.
4. Any line of endocrine-based therapy for inoperable locally advanced or metastatic disease.

Where this trial is running

Tucson, Arizona and 282 other locations

+233 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Locally Advanced or Metastatic Breast CancerLocally advanced or Metastatic Breast Cancer
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.