SOLTI launches HARMONIA, an international phase III study to identify the best therapeutic option for selected patients with aggressive HR+/HER2- advanced breast cancer

Barcelona, 17 September 2021.- SOLTI launches HARMONIA, the first phase III clinical trial that will compare treatment options for patients with difficult-to-treat hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). There is an unmet patient need to understand the optimal treatment approach for patients with HER2-enriched (HER2-E) disease, a subtype associated with a very poor prognosis and endocrine-resistance, compared to luminal disease. 

HARMONIA is the first phase III trial to select patients based on their tumor´s RNA-based molecular subtype. It will be one of the most important clinical and translational prospective research efforts ever conducted to help understand specific subgroups of patients with advanced HR+/HER2- ABC. HARMONIA will provide both a better understanding of the biological heterogeneity of these tumors as well as insights into changes that can occur over time under specific therapies. The study will be conducted in Spain, Portugal and the United States, with the participation of 80 hospitals, and more than 500 patients will be included. HARMONIA will be led by SOLTI in collaboration with the US-based Alliance Foundation Trials organization and Novartis Pharma AG.

The primary objective of the study is to test the value of two CDK4/6 inhibitors in patients with the HER2-E subtype. This particular subtype represents 10-20% of HR+/HER2- ABC patients and is associated with poor response and survival if treated with endocrine therapy (ET)-only. In this group of patients, ribociclib, a CDK4/6 inhibitor, has demonstrated pronounced efficacy in a large retrospective analysis of 3 phase III clinical trials. Now, HARMONIA will test the hypothesis prospectively that ribociclib may improve the course of HR+/HER2- disease by changing the tumor biology, enabling a better response to endocrine therapy compared to palbociclib, another approved CDK4/6 inhibitor. This may further substantiate differences seen with CDK4/6 inhibitors in demonstrating overall survival benefit.

Additionally, the study will offer therapy with a chemotherapy-based regimen to patients with the Basal-like subtype, a subgroup representing 3-5% of patients with HR+/HER2- ABC. Patients with this tumor biology, which behaves more like a triple-negative breast cancer, typically face a very poor prognosis when treated with endocrine-based therapies.

In the last 5 years, SOLTI has focused on studying breast cancer at the RNA level to demonstrate the prognostic and predictive value of the 4 molecular subtypes and has run small prospective studies pre-selecting patients based on their RNA-based profile. Screening approximately 2,500 patients through HARMONIA with HR+/HER2- ABC, who represent 70% of all patients with ABC, marks a tremendous advancement. As stated by Aleix Prat, SOLTI´s President, Head of the Medical Oncology Department at Hospital Clínic of Barcelona, Head of the Translational Genomics Group and Targeted Therapies in Solid Tumors at IDIBAPS and Professor of Medicine at the University of Barcelona, “HARMONIA is the consequence of many years of research in the field of RNA-based profiling and metastatic breast cancer. We are very proud to conduct this huge clinical and translational effort to improve the diagnosis and treatment of patients who suffer this devastating disease”. 

Aleix Prat, MD PhD, SOLTI President and Head of the Medical Oncology Department and Translational Genomics & Targeted Therapeutics Group at the Hospital Clinic Barcelona (Barcelona, ESP), along with Lisa A. Carey, MD ScM, co-Chair of the Breast Cancer Committee at the ALLIANCE and Deputy Director of Clinical Science at Lineberger Comprehensive Cancer Center (Chapel Hill, NC, US), will provide leadership for HARMONIA. Daniel Stover, MD, Assistant Professor of Medicine at Ohio State University College of Medicine and Medical Oncologist at the Stefanie Spielman Comprehensive Breast Center (Columbus, OH, US) and Tomás Pascual, MD, Medical Oncologist and Chief Scientific Officer at SOLTI, will also co-lead the project and serve as study chairs. 

It is anticipated that HARMONIA will recruit the first patient in March 2022 and the trial will last for 5 years.