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

April 24, 2025 updated by: SOLTI Breast Cancer Research Group

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

456

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Portugal
      • Creixomil, Portugal
        • Hospital Senhora da Oliveira - Guimarães
      • Lisboa, Portugal, 1500-650
        • Ipo Lisboa
      • Loures, Portugal, 2674-514
        • Hospital Beatriz Angelo
      • Porto, Portugal, 4200-072
        • Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE
      • Vila Nova de Gaia, Portugal, 4434-502
        • Centro Hospitalar Vila Nova de Gaia
  • Spain
      • Alicante, Spain, 03010
        • Hospital General Universitario de Alicante
      • Barcelona, Spain, 08003
        • Hospital del Mar
      • Barcelona, Spain, 08036
        • Hospital Clinic De Barcelona
      • Barcelona, Spain, 08035
        • Vall d´Hebron University Hospital
      • Barcelona, Spain, 8023
        • IOB-Institute of Oncology. Hospital Quironsalud Barcelona
      • Bilbao, Spain, 48013
        • Hospital de Basurto
      • Cáceres, Spain, 10003
        • Complejo Hospitalario San Pedro de Alcántara
      • Girona, Spain, 17007
        • Institut Català d' Oncologia de Girona (ICO Girona)
      • Granada, Spain, 18014
        • Hospital Universitario Virgen De Las Nieves
      • Granada, Spain, 18016
        • H. Clínico San Cecilio de Granada
      • Las Palmas, Spain, 35010
        • Hospital Universitario de Gran Canaria Doctor Negrin
      • León, Spain, 24001
        • Complejo Asistencial Universitario de Leon
      • Lleida, Spain, 25198
        • Hospital Universitari Arnau de Vilanova de Lleida
      • Madrid, Spain, 28040
        • Fundación Jiménez Díaz
      • Madrid, Spain, 28006
        • Hospital Universitario La Princesa
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28046
        • Hospital La Paz
      • Madrid, Spain, 28050
        • Centro Integral Oncológico Clara Campal (CIOCC)
      • Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro de Majadahonda
      • Malaga, Spain, 29010
        • Hospital Virgen de la Victoria
      • Murcia, Spain, 30008
        • Hospital Universitario Morales Meseguer
      • Reus, Spain, 43204
        • Hospital Sant Joan de Reus
      • Salamanca, Spain, 37007
        • Hospital Universitario de Salamanca
      • Santander, Spain, 39008
        • Hospital Universitario Marqués de Valdecilla
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio
      • Sevilla, Spain, 41007
        • Hospital Virgen De La Macarena
      • Sevilla, Spain, 41013
        • Hospital Quiron Salud Sagrado Corazon Sevilla
      • Valencia, Spain, 46010
        • Hospital Clinico Universitario de Valencia
      • Valencia, Spain, 46009
        • Instituto Valenciano de Oncologia (IVO)
      • Zaragoza, Spain, 50009
        • Hospital Clinico Universitario Lozano Blesa
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Institut Català d' Oncologia (ICO Badalona)
      • Hospitalet de Llobregat, Barcelona, Spain, 08908
        • Institut Català d'Oncologia (ICO Hospitalet)
      • Sant Cugat Del Vallès, Barcelona, Spain, 08195
        • Hospital General de Catalunya
    • Illes Balears
      • Palma de Mallorca, Illes Balears, Spain, 07198
        • Hospital Son Llatzer
    • Islas Canarias
      • Tenerife, Islas Canarias, Spain, 38320
        • Hospital Universitario de Canarias
    • La Coruña
      • A Coruña, La Coruña, Spain, 15006
        • Hospital Clínico Universitario de A Coruña
      • Santiago De Compostela, La Coruña, Spain, 15706
        • Hospital Clínico Universitario de Santiago CHUS
    • Madrid
      • Fuenlabrada, Madrid, Spain, 28942
        • Hospital Universitario de Fuenlabrada
    • Murcia
      • El Palmar, Murcia, Spain, 30120
        • Hospital Universitario Virgen de la Arrixaca
  • United States
    • Florida
      • Clearwater, Florida, United States, 33756
        • Morton Plant Hospital
      • Coral Gables, Florida, United States, 33124
        • University of Miami
      • Hollywood, Florida, United States, 33021
        • Memorial Regional Hospital
      • Miami, Florida, United States, 33140
        • Mount Sinai Florida
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky, Markey Cancer Center
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Sinai of Baltimore
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Faber Cancer Institute
    • Mississippi
      • Oxford, Mississippi, United States, 38655
        • Baptist Memorial Health Care
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • Nevada
      • Las Vegas, Nevada, United States, 89121
        • Nevada Cancer Research Foundation
    • New Hampshire
      • Londonderry, New Hampshire, United States, 03053
        • NHOH
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore
      • New York, New York, United States, 11042-1069
        • Nothwell Health
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina Lineberger
      • Winston-Salem, North Carolina, United States, 27103
        • Novant Health Care
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State University Comprehensive Cancer Center
      • Kettering, Ohio, United States, 45429
        • Dayton Clinical Oncology
    • Oregon
      • Portland, Oregon, United States, 97225
        • Providence Portland Medical Center
      • Portland, Oregon, United States, 97210
        • Legacy Good Samaritan Hospital and Medical Cente
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • The Medical University of South Carolina
      • Spartanburg, South Carolina, United States, 29302
        • Upstate Carolina Medical Center
    • Virginia
      • Huntington, Virginia, United States, 25701
        • Edwards Comprehensive Cancer Center
      • Mechanicsville, Virginia, United States, 231136
        • Bon Secours Memorial Regional Medical Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • Unv. Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ribociclib + Endocrine Therapy
Ribociclib + Fulvestrant or Letrozole
Drug: Ribociclib + Letrozole OR Fulvestrant
Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
Experimental: Palbociclib + Endocrine Therapy
Palbociclib + Fulvestrant or Letrozole
Drug: Palbociclib + Letrozole OR Fulvestrant
Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
Experimental: Paclitaxel +/- Tislelizumab - Exploratory cohort
Additional experimental Cohort that includes patients with Basal-Like intrinsic subtype.
Drug: Paclitaxel +/- Tislelizumab
Patients in this arm could receive as the first line of therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
using RECIST 1.1 criteria, as assessed by local radiologists/investigators
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival 2
Time Frame: 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
defined as the time from randomization to first documented progression on next-line therapy or death, whichever occurs first
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
Overall Survival
Time Frame: until patient death, assessed up to approximately 62 months after the first patient enrolled
the proportion of exitus patients
until patient death, assessed up to approximately 62 months after the first patient enrolled
Overall response and clinical benefit
Time Frame: until disease progression or 24 weeks from treatment start.
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.
until disease progression or 24 weeks from treatment start.
Time to response and duration of response
Time Frame: time from treatment start to response and time from response to disease progression, assessed up to approximately 62 months after the first patient enrolled
defined per RECIST 1.1
time from treatment start to response and time from response to disease progression, assessed up to approximately 62 months after the first patient enrolled
Adverse events (safety)
Time Frame: from randomization/enrollment to end of study assessed up to approximately 62 months after the first patient enrolled
Occurrence /severity of AEs, laboratory abnormalities, discontinuation rates, dose reductions/interruptions
from randomization/enrollment to end of study assessed up to approximately 62 months after the first patient enrolled

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

SOLTI Breast Cancer Research Group

Collaborators

Novartis
Alliance Foundation Trials, LLC.

Investigators

  • Principal Investigator: Aleix Prat, MD, Hospital Clínic of Barcelona / SOLTI
  • Principal Investigator: Lisa A Carey, MD, UNC Lineberger Comprehensive Cancer Center
  • Principal Investigator: Dan G Stover, MD, Stefanie Spielman Comprehensive Breast Center
  • Principal Investigator: Tomás Pascual, MD, Hospital Clínic of Barcelona / SOLTI cancer research group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 28, 2022

Primary Completion (Estimated)

March 1, 2026

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

January 4, 2022

First Submitted That Met QC Criteria

January 12, 2022

First Posted (Actual)

January 26, 2022

Study Record Updates

Last Update Posted (Actual)

April 29, 2025

Last Update Submitted That Met QC Criteria

April 24, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SOLTI-2101
  • 2021-002027-38 (EudraCT Number)
  • LEE011A2303R (Other Identifier: Novartis)
  • AFT-58 (Other Identifier: Alliance Foundation Trials, LLC)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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