NCT05207709: HARMONIA

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

Active, enrolled Phase 3 Last updated 29 April 2025

What this trial tests

Phase 3 trial testing Ribociclib + Letrozole OR Fulvestrant in Metastatic Breast Cancer in 456 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

28 March 2022

Primary endpoint
1 March 2026

1 March 2027

Quick facts

Lead sponsor	SOLTI Breast Cancer Research Group
Phase	Phase 3
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	456
Start date	28 March 2022
Primary completion	1 March 2026
Estimated completion	1 March 2027
Sites	71 locations across Portugal, United States, Spain

Drugs / interventions tested

• Ribociclib + Letrozole OR Fulvestrant — full drug profile →
• Palbociclib + Letrozole OR Fulvestrant — full drug profile →
• Paclitaxel +/- Tislelizumab — full drug profile →

Conditions studied

• Metastatic Breast Cancer — all drugs for Metastatic Breast Cancer →

Sponsor

SOLTI Breast Cancer Research Group

Who can join

18 and older, any sex, with Metastatic Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. 6th and 7th International consensus guidelines for the management of advanced breast cancer (ABC guidelines 6 and 7).
   Cardoso F, Paluch-Shimon S, Schumacher-Wulf E, Matos L, et al · · 2024 · cited 136× · PMID 38896983 · DOI 10.1016/j.breast.2024.103756
2. Abemaciclib, Palbociclib, and Ribociclib in Real-World Data: A Direct Comparison of First-Line Treatment for Endocrine-Receptor-Positive Metastatic Breast Cancer.
   Cejuela M, Gil-Torralvo A, Castilla MÁ, Domínguez-Cejudo MÁ, et al · · 2023 · cited 48× · PMID 37239834 · DOI 10.3390/ijms24108488
3. Circulating tumor DNA reveals complex biological features with clinical relevance in metastatic breast cancer.
   Prat A, Brasó-Maristany F, Martínez-Sáez O, Sanfeliu E, et al · · 2023 · cited 41× · PMID 36859416 · DOI 10.1038/s41467-023-36801-9
4. The dilemma of selecting a first line CDK4/6 inhibitor for hormone receptor-positive/HER2-negative metastatic breast cancer.
   Grinshpun A, Tolaney SM, Burstein HJ, Jeselsohn R, et al · · 2023 · cited 31× · PMID 36949066 · DOI 10.1038/s41523-023-00520-7
5. CDK4/6 Inhibitors-Overcoming Endocrine Resistance Is the Standard in Patients with Hormone Receptor-Positive Breast Cancer.
   Nabieva N, Fasching PA. · · 2023 · cited 20× · PMID 36980649 · DOI 10.3390/cancers15061763
6. Moving toward precision medicine to predict drug sensitivity in patients with metastatic breast cancer.
   Bottosso M, Mosele F, Michiels S, Cournède PH, et al · · 2024 · cited 17× · PMID 38401248 · DOI 10.1016/j.esmoop.2024.102247
7. How I treat endocrine-dependent metastatic breast cancer.
   Gombos A, Goncalves A, Curigliano G, Bartsch R, et al · · 2023 · cited 16× · PMID 36806375 · DOI 10.1016/j.esmoop.2023.100882
8. Intrinsic Subtype and Overall Survival of Patients with Advanced HR+/HER2- Breast Cancer Treated with Ribociclib and ET: Correlative Analysis of MONALEESA-2, -3, -7.
   Prat A, Solovieff N, André F, O'Shaughnessy J, et al · · 2024 · cited 14× · PMID 37939142 · DOI 10.1158/1078-0432.ccr-23-0561