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Metastatic Breast CancerPhase 3HARMONIANCT05207709

Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype

A Phase 3 study testing Ribociclib + Letrozole OR Fulvestrant, Palbociclib + Letrozole OR Fulvestrant and Paclitaxel +/- Tislelizumab in people with Metastatic Breast Cancer, run by SOLTI Breast Cancer Research Group at 71 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

HARMONIA is an international, multicenter, randomized, open-label and phase III study. The primary objective of this study is to demonstrate that the combination of ribociclib with endocrine therapy (letrozole or fulvestrant) is superior to palbociclib with endocrine therapy (letrozole or fulvestrant) in prolonging… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Ribociclib + Letrozole OR Fulvestrant, Palbociclib + Letrozole OR Fulvestrant and Paclitaxel +/- Tislelizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
61 participants
Where
71 sitesin 3 countries
Study dates
28 Mar 2022to 26 Mar 2026
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Main Inclusion Criteria:

  • Histologically documented HR-positive and HER2-negative breast cancer by local testing
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
  • Availability of FFPE tumor block for biomarker analysis, obtained during metastatic period.
  • HER2-E or Basal-like subtype as per central PAM50 analysis.
  • Measurable disease or non-measurable disease, as defined by RECIST v1.1
  • Adequate hematologic and end-organ function
  • Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
  • Women of childbearing potential must have confirmed negative serum pregnancy test within 7 days prior to randomization.
  • Women of CBP must be willing to use highly effective methods of contraception.
  • Patient must have a 6-lead or 12-lead ECG with ALL of the following parameters at screening:
  • QTcF interval (QT interval using Fridericia's correction) at screening < 450 msec.
  • Resting heart rate 50-90 beats per minute (determined from the ECG).

Main Exclusion Criteria:

  • Prior therapy with any CDK4/6 inhibitors.
  • Patient has received prior treatment with chemotherapy for advanced/metastatic breast cancer

Trial locations and contacts

71 sites in 3 countries.

71 sites in 3 countries

Spain40 sites

  • Hospital Clínico Universitario de A Coruña

    A Coruña, La Coruña, 15006

  • Hospital General Universitario de Alicante

    Alicante, 03010

  • Institut Català d' Oncologia (ICO Badalona)

    Badalona, Barcelona, 08916

  • Hospital del Mar

    Barcelona, Barcelona, 08003

  • IOB-Institute of Oncology. Hospital Quironsalud Barcelona

    Barcelona, Barcelona, 8023

  • Vall d´Hebron University Hospital

    Barcelona, 08035

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Hospital de Basurto

    Bilbao, 48013

  • Complejo Hospitalario San Pedro de Alcántara

    Cáceres, 10003

  • Hospital Universitario Virgen de la Arrixaca

    El Palmar, Murcia, 30120

  • Hospital Universitario de Fuenlabrada

    Fuenlabrada, Madrid, 28942

  • Institut Català d' Oncologia de Girona (ICO Girona)

    Girona, Girona, 17007

  • Hospital Universitario Virgen de las Nieves

    Granada, 18014

  • H. Clínico San Cecilio de Granada

    Granada, 18016

  • Institut Català d'Oncologia (ICO Hospitalet)

    L'Hospitalet de Llobregat, Barcelona, 08908

  • Hospital Universitario de Gran Canaria Doctor Negrin

    Las Palmas, 35010

  • Complejo Asistencial Universitario de León

    León, León, 24001

  • Hospital Universitari Arnau de Vilanova de Lleida

    Lleida, 25198

  • Hospital Universitario Ramón y Cajal

    Madrid, Madrid, 28034

  • Fundación Jiménez Díaz

    Madrid, Madrid, 28040

  • Hospital La Paz

    Madrid, Madrid, 28046

  • Hospital Universitario La Princesa

    Madrid, 28006

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Centro Integral Oncológico Clara Campal (CIOCC)

    Madrid, 28050

  • Hospital Universitario Puerta de Hierro de Majadahonda

    Madrid, 28222

  • Hospital Virgen de la Victoria

    Málaga, 29010

  • Hospital Universitario Morales Meseguer

    Murcia, Murcia, 30008

  • Hospital Son Llàtzer

    Palma de Mallorca, Balearic Islands, 07198

  • Hospital Sant Joan de Reus

    Reus, 43204

  • Hospital Universitario de Salamanca

    Salamanca, 37007

  • Hospital General de Catalunya

    Sant Cugat del Vallès, Barcelona, 08195

  • Hospital Universitario de Canarias

    Santa Cruz de Tenerife, Canary Islands, 38320

  • Hospital Universitario Marqués de Valdecilla

    Santander, 39008

  • Hospital Clínico Universitario de Santiago CHUS

    Santiago de Compostela, La Coruña, 15706

  • Hospital Quiron Salud Sagrado Corazon Sevilla

    Seville, Sevilla, 41013

  • Hospital Universitario Virgen del Rocio

    Seville, Sevilla, 41013

  • Hospital Virgen de la Macarena

    Seville, 41007

  • Instituto Valenciano de Oncología (IVO)

    Valencia, 46009

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza, Zaragoza, 50009

Other trials in Spain

United States26 sites

  • Sinai of Baltimore

    Baltimore, Maryland, 21215

  • Dana Faber Cancer Institute

    Boston, Massachusetts, 02215

  • University of North Carolina Lineberger

    Chapel Hill, North Carolina, 27514

  • The Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Northwestern

    Chicago, Illinois, 60611

  • Morton Plant Hospital

    Clearwater, Florida, 33756

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • University of Miami

    Coral Gables, Florida, 33124

  • Memorial Regional Hospital

    Hollywood, Florida, 33021

  • Edwards Comprehensive Cancer Center

    Huntington, Virginia, 25701

  • Dayton Clinical Oncology

    Kettering, Ohio, 45429

  • Nevada Cancer Research Foundation

    Las Vegas, Nevada, 89121

  • University of Kentucky, Markey Cancer Center

    Lexington, Kentucky, 40536

  • NHOH

    Londonderry, New Hampshire, 03053

  • Unv. Wisconsin

    Madison, Wisconsin, 53792

  • Bon Secours Memorial Regional Medical Center

    Mechanicsville, Virginia, 231136

  • Mount Sinai Florida

    Miami, Florida, 33140

  • Nothwell Health

    New York, New York, 11042-1069

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Baptist Memorial Health Care

    Oxford, Mississippi, 38655

  • Legacy Good Samaritan Hospital and Medical Cente

    Portland, Oregon, 97210

  • Providence Portland Medical Center

    Portland, Oregon, 97225

  • Upstate Carolina Medical Center

    Spartanburg, South Carolina, 29302

  • Montefiore

    The Bronx, New York, 10467

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Novant Health Care

    Winston-Salem, North Carolina, 27103

Other trials in United States

Portugal5 sites

  • Hospital Senhora da Oliveira - Guimarães

    Creixomil

  • IPO Lisboa

    Lisbon, 1500-650

  • Hospital Beatriz Ângelo

    Loures, 2674-514

  • Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE

    Porto, 4200-072

  • Centro Hospitalar Vila Nova de Gaia

    Vila Nova de Gaia, 4434-502

Other trials in Portugal

About this study

Official title: A Phase III, Multicenter, Open-label Study of Ribociclib vs. Palbociclib in Patients With Advanced Hormone Receptor-positive/HER2-negative/HER2-Enriched Breast Cancer - HARMONIA Trial

HARMONIA is an international, multicenter, randomized, open-label and phase III study. The primary objective of this study is to demonstrate that the combination of ribociclib with endocrine therapy (letrozole or fulvestrant) is superior to palbociclib with endocrine therapy (letrozole or fulvestrant) in prolonging progression-free survival in patients with advanced HR+/HER2- and HER2-E breast cancer. The study will enroll approximately 456 patients with HER2-E disease from approximately 95 sites worldwide.

In addition, the HARMONIA trial will include an exploratory cohort of patients with HR+/HER2- and Basal-like disease treated with paclitaxel +/- Tislelizumab. This cohort does not have a predefined sample size and the objective is only exploratory, given the suggested lack of efficacy of the combinations of hormone therapy and CDK4/6 inhibitors in this subgroup of patients. Enrolment into the basal-like cohort will stop once the HER2-E disease cohort is fully enrolled.

Being tested
Ribociclib + Letrozole OR Fulvestrant, Palbociclib + Letrozole OR Fulvestrant, Paclitaxel +/- Tislelizumab
Keywords
PAM50, intrinsic subtype, HER2-Enriched
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ribociclib + Letrozole OR FulvestrantDrug

    Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks

  • Palbociclib + Letrozole OR FulvestrantDrug

    Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks

  • Paclitaxel +/- TislelizumabDrug

    Patients in this arm could receive as the first line of therapy

Study groups in NCT05207709
Study groupRoleWhat they receive
Ribociclib + Endocrine TherapyExperimentalRibociclib + Fulvestrant or Letrozole
Receives: Drug: Ribociclib + Letrozole OR Fulvestrant
Palbociclib + Endocrine TherapyExperimentalPalbociclib + Fulvestrant or Letrozole
Receives: Drug: Palbociclib + Letrozole OR Fulvestrant
Paclitaxel +/- Tislelizumab - Exploratory cohortExperimentalAdditional experimental Cohort that includes patients with Basal-Like intrinsic subtype.
Receives: Drug: Paclitaxel +/- Tislelizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival

    using RECIST 1.1 criteria, as assessed by local radiologists/investigators

    Measured: From date of randomization until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 62 months after the first patient enrolled

Secondary outcomes (5)

  1. Progression-free survival 2

    defined as the time from randomization to first documented progression on next-line therapy or death, whichever occurs first

    Measured: From randomization until documented progression to second line of therapy, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 62 months after the first patient enrolled

  2. Overall Survival

    the proportion of exitus patients

    Measured: until patient death, assessed up to approximately 62 months after the first patient enrolled

  3. Overall response and clinical benefit

    defined as percentage of patients with CR, PR per RECIST 1.1 or SD lasting 24 weeks or longer, as defined by RECIST 1.1.

    Measured: until disease progression or 24 weeks from treatment start.

  4. Time to response and duration of response

    defined per RECIST 1.1

    Measured: time from treatment start to response and time from response to disease progression, assessed up to approximately 62 months after the first patient enrolled

  5. Adverse events (safety)

    Occurrence /severity of AEs, laboratory abnormalities, discontinuation rates, dose reductions/interruptions

    Measured: from randomization/enrollment to end of study assessed up to approximately 62 months after the first patient enrolled

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2022
  2. Study start28 Mar 2022
  3. Primary completion26 Mar 2026
  4. Study completion26 Mar 2026

Why it stopped: The study was prematurely halted because enrollment was significantly delayed compared with the original projections due to the evolving therapeutic landscape.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
61 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05207709
Sponsor's protocol ID
SOLTI-2101
Other IDs
2021-002027-38, LEE011A2303R, AFT-58
Acronym
HARMONIA
Status last verified
Apr 2025
First submitted
4 Jan 2022
Last updated
25 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kalinsky K, Accordino MK, Chiuzan C, Mundi PS, Sakach E, Sathe C, Ahn H, Trivedi MS, Novik Y, Tiersten A, Raptis G, Baer LN, Oh SY, Zelnak AB, Wisinski KB, Andreopoulou E, Gradishar WJ, Stringer-Reasor E, Reid SA, O'Dea A, O'Regan R, Crew KD, Hershman DL. Randomized Phase II Trial of Endocrine Therapy With or Without Ribociclib After Progression on Cyclin-Dependent Kinase 4/6 Inhibition in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: MAINTAIN Trial. J Clin Oncol. 2023 Aug 20;41(24):4004-4013. doi: 10.1200/JCO.22.02392. Epub 2023 May 19.

    PubMed 37207300

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ribociclib + Letrozole OR Fulvestrant, Palbociclib + Letrozole OR Fulvestrant and Paclitaxel +/- Tislelizumab in people with Metastatic Breast Cancer, run by SOLTI Breast Cancer Research Group at 71 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 71 sites in Spain, United States, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was prematurely halted because enrollment was significantly delayed compared with the original projections due to the evolving therapeutic landscape.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (time frame: From date of randomization until the date of first documented progression, death, lost of follow-up, withdraw consent or the study is terminated by SOLTI, whichever occurs first, assessed up to approximately 62 months after the first patient enrolled). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05207709, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2026.

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