NEW YORK – Novartis on Sunday said it would work with SOLTI Innovative Cancer Research to conduct HARMONIA, an international, randomized, Phase III trial comparing the efficacy of ribociclib (Kisqali) against palbociclib (Pfizer's Ibrance) in hormone receptor (HR)-positive HER2-negative, metastatic breast cancer patients with a HER2-enriched intrinsic subtype.
According to Novartis, this is the first trial in which the two competing CDK4/6 inhibitors, ribociclib and palbociclib, will be directly compared in HR-positive HER2-negative advanced breast cancer. Both drugs will be given to patients in combination with endocrine therapy. Additionally, breast cancer patients with HR-positive HER2-negative tumors that are HER2 enriched will be selected for enrollment using RNA-based molecular subtyping.
The overarching categorization of breast tumors are dictated by their HR status (estrogen and progesterone receptors) and level of HER2 expression typically assessed using immunohistochemistry and fluorescent in situ hybridization. More recently, researchers have further classified tumors according to five intrinsic subtypes: luminal A, luminal B, HER2-enriched, claudin-low, and basal-like. HER2-enriched tumors have distinct transcriptional features that have been observed in all breast tumor types, not just tumors with HER2 overexpression determined by standard tests.
SOLTI Innovative Cancer Research, a nonprofit clinical and translational research group, is leading HARMONIA in collaboration with Novartis and Alliance Foundation Trials and will conduct the study across 80 hospitals in Spain, Portugal, and the US. Aleix Prat, SOLTI president and head of the medical oncology department at Hospital Clínic of Barcelona, said in a statement that HARMONIA investigators will conduct "first-of-a-kind research on breast cancer at the RNA level to recognize the value of intrinsic subtypes, which impacts patient outcomes in terms of incidence, survival, and response to treatment."
Within HARMONIA, researchers are particularly interested in gauging whether ribociclib alters tumor biology and enables patients to respond better to it than palbociclib. The primary endpoint in the study is progression-free survival. Enrollment is slated to begin in Q1 2022.
According to Novartis, investigators may also enroll patients with the basal-like subtype as an exploratory cohort in the trial and treat them with a chemotherapy-based regimen, since basal-like tumors have similarities to triple-negative breast cancer.
Novartis has documented ribociclib's overall survival impact on breast cancer patients across the MONALEESA research program. The drug is available as an initial endocrine-based therapy with an aromatase inhibitor in the US and Europe for pre-, peri-, and postmenopausal women with HR-positive HER2-negative, locally advanced or metastatic breast cancer.