Ribociclib vs. Palbociclib in Patients With Advanced Breast Cancer Within the HER2-Enriched Intrinsic Subtype
HARMONIA
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
4 other identifiers
interventional
456
3 countries
71
Brief 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 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2022
Longer than P75 for phase_3
71 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 4, 2022
CompletedFirst Posted
Study publicly available on registry
January 26, 2022
CompletedStudy Start
First participant enrolled
March 28, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2027
ExpectedApril 29, 2025
April 1, 2025
3.9 years
January 4, 2022
April 24, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free survival
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 Outcomes (5)
Progression-free survival 2
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
until patient death, assessed up to approximately 62 months after the first patient enrolled
Overall response and clinical benefit
until disease progression or 24 weeks from treatment start.
Time to response and duration of response
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)
from randomization/enrollment to end of study assessed up to approximately 62 months after the first patient enrolled
Study Arms (3)
Ribociclib + Endocrine Therapy
EXPERIMENTALRibociclib + Fulvestrant or Letrozole
Palbociclib + Endocrine Therapy
EXPERIMENTALPalbociclib + Fulvestrant or Letrozole
Paclitaxel +/- Tislelizumab - Exploratory cohort
EXPERIMENTALAdditional experimental Cohort that includes patients with Basal-Like intrinsic subtype.
Interventions
Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
Endocrine Therapy will be selected by the investigator. For premenopausal women and men: LHRH agonist once every 4 weeks
Patients in this arm could receive as the first line of therapy
Eligibility Criteria
You may qualify if:
- 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).
You may not qualify if:
- Prior therapy with any CDK4/6 inhibitors.
- Patient has received prior treatment with chemotherapy for advanced/metastatic breast cancer
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- SOLTI Breast Cancer Research Grouplead
- Novartiscollaborator
- Alliance Foundation Trials, LLC.collaborator
Study Sites (71)
Morton Plant Hospital
Clearwater, Florida, 33756, United States
University of Miami
Coral Gables, Florida, 33124, United States
Memorial Regional Hospital
Hollywood, Florida, 33021, United States
Mount Sinai Florida
Miami, Florida, 33140, United States
Northwestern
Chicago, Illinois, 60611, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
University of Kentucky, Markey Cancer Center
Lexington, Kentucky, 40536, United States
Sinai of Baltimore
Baltimore, Maryland, 21215, United States
Dana Faber Cancer Institute
Boston, Massachusetts, 02215, United States
Baptist Memorial Health Care
Oxford, Mississippi, 38655, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Nevada Cancer Research Foundation
Las Vegas, Nevada, 89121, United States
NHOH
Londonderry, New Hampshire, 03053, United States
Nothwell Health
New York, New York, 11042-1069, United States
Montefiore
The Bronx, New York, 10467, United States
University of North Carolina Lineberger
Chapel Hill, North Carolina, 27514, United States
Novant Health Care
Winston-Salem, North Carolina, 27103, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Dayton Clinical Oncology
Kettering, Ohio, 45429, United States
Legacy Good Samaritan Hospital and Medical Cente
Portland, Oregon, 97210, United States
Providence Portland Medical Center
Portland, Oregon, 97225, United States
The Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Upstate Carolina Medical Center
Spartanburg, South Carolina, 29302, United States
Edwards Comprehensive Cancer Center
Huntington, Virginia, 25701, United States
Bon Secours Memorial Regional Medical Center
Mechanicsville, Virginia, 231136, United States
Unv. Wisconsin
Madison, Wisconsin, 53792, United States
Hospital Senhora da Oliveira - Guimarães
Creixomil, Portugal
IPO Lisboa
Lisbon, 1500-650, Portugal
Hospital Beatriz Ângelo
Loures, 2674-514, Portugal
Instituto Portugues de Oncologia de Porto Francisco Gentil, EPE
Porto, 4200-072, Portugal
Centro Hospitalar Vila Nova de Gaia
Vila Nova de Gaia, 4434-502, Portugal
Hospital Son Llàtzer
Palma de Mallorca, Balearic Islands, 07198, Spain
Institut Català d' Oncologia (ICO Badalona)
Badalona, Barcelona, 08916, Spain
Hospital del Mar
Barcelona, Barcelona, 08003, Spain
IOB-Institute of Oncology. Hospital Quironsalud Barcelona
Barcelona, Barcelona, 8023, Spain
Institut Català d'Oncologia (ICO Hospitalet)
L'Hospitalet de Llobregat, Barcelona, 08908, Spain
Hospital General de Catalunya
Sant Cugat del Vallès, Barcelona, 08195, Spain
Hospital Universitario de Canarias
Santa Cruz de Tenerife, Canary Islands, 38320, Spain
Institut Català d' Oncologia de Girona (ICO Girona)
Girona, Girona, 17007, Spain
Hospital Clínico Universitario de A Coruña
A Coruña, La Coruña, 15006, Spain
Hospital Clínico Universitario de Santiago CHUS
Santiago de Compostela, La Coruña, 15706, Spain
Complejo Asistencial Universitario de León
León, León, 24001, Spain
Hospital Universitario de Fuenlabrada
Fuenlabrada, Madrid, 28942, Spain
Hospital Universitario Ramón y Cajal
Madrid, Madrid, 28034, Spain
Fundación Jiménez Díaz
Madrid, Madrid, 28040, Spain
Hospital La Paz
Madrid, Madrid, 28046, Spain
Hospital Universitario Virgen de la Arrixaca
El Palmar, Murcia, 30120, Spain
Hospital Universitario Morales Meseguer
Murcia, Murcia, 30008, Spain
Hospital Quiron Salud Sagrado Corazon Sevilla
Seville, Sevilla, 41013, Spain
Hospital Universitario Virgen del Rocio
Seville, Sevilla, 41013, Spain
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Zaragoza, 50009, Spain
Hospital General Universitario de Alicante
Alicante, 03010, Spain
Vall d´Hebron University Hospital
Barcelona, 08035, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital de Basurto
Bilbao, 48013, Spain
Complejo Hospitalario San Pedro de Alcántara
Cáceres, 10003, Spain
Hospital Universitario Virgen de las Nieves
Granada, 18014, Spain
H. Clínico San Cecilio de Granada
Granada, 18016, Spain
Hospital Universitario de Gran Canaria Doctor Negrin
Las Palmas, 35010, Spain
Hospital Universitari Arnau de Vilanova de Lleida
Lleida, 25198, Spain
Hospital Universitario La Princesa
Madrid, 28006, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
Centro Integral Oncológico Clara Campal (CIOCC)
Madrid, 28050, Spain
Hospital Universitario Puerta de Hierro de Majadahonda
Madrid, 28222, Spain
Hospital Virgen de la Victoria
Málaga, 29010, Spain
Hospital Sant Joan de Reus
Reus, 43204, Spain
Hospital Universitario de Salamanca
Salamanca, 37007, Spain
Hospital Universitario Marqués de Valdecilla
Santander, 39008, Spain
Hospital Virgen de la Macarena
Seville, 41007, Spain
Instituto Valenciano de Oncología (IVO)
Valencia, 46009, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Related Publications (1)
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.
PMID: 37207300DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- 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
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 4, 2022
First Posted
January 26, 2022
Study Start
March 28, 2022
Primary Completion
March 1, 2026
Study Completion (Estimated)
March 1, 2027
Last Updated
April 29, 2025
Record last verified: 2025-04
Data Sharing
- IPD Sharing
- Will not share