Kisqali (ribociclib)

P2, N=80, Recruiting, Hoffmann-La Roche | N=44 --> 80 | Trial completion date: Dec 2030 --> Feb 2030

P3, N=300, Not yet recruiting, Rovi Pharmaceuticals Laboratories | Trial completion date: Jun 2031 --> Dec 2033 | Initiation date: May 2026 --> Aug 2026

P2/3, N=316, Completed, Solti Group | Active, not recruiting --> Completed

P2, N=38, Recruiting, Hoffmann-La Roche | N=14 --> 38

P2, N=60, Recruiting, Hoffmann-La Roche | Active, not recruiting --> Recruiting

In exploratory prospective studies, our system predicted ribociclib-induced grade 3 DILI in one ER+/HER2- breast cancer patient and absence of DILI in two patients, consistent with clinical outcomes. These findings highlight the value of integrating our model with our AI-based mapping strategy to enable mechanistic classification of DILI, deconvolution of immune-related toxicity, and prediction of patient-specific risk. Our platform represents a step toward personalized hepatotoxicity assessment and improved translational toxicology strategies.

P3, N=193, Recruiting, Eli Lilly and Company

Patients who receive CDK4/6 inhibitors for breast cancer experience a low but measurable risk of new-onset atrial arrhythmias. There was no significant difference in new-onset AA risk between agents. Prospective studies are needed to define mechanisms and guide monitoring strategies.

This two-center retrospective study included 203 patients with HR+/HER2- MBC who received first-line CDK4/6 inhibitors (ribociclib or palbociclib) plus endocrine therapy between 2018 and 2024. Although the predictive accuracy of ΔSUVmax alone was modest, the strong survival gradient suggests meaningful prognostic value. Prospective studies with standardized imaging time points and comprehensive metabolic metrics are warranted to define the role of PET-guided treatment adaptation.

PBPK modeling predicted that ritonavir or erythromycin (strong and moderate CYP3A4 inhibitors) would increase ribociclib steady-state area under the concentration-time curve (AUC) by 1.84-fold or show no meaningful impact, respectively. Steady-state ribociclib AUC was estimated to decrease by 83% and 74% with rifampicin and efavirenz, strong and moderate CYP3A4 inducers, respectively. Ribociclib was estimated to increase CYP3A4 substrate midazolam exposure by 280%. Mild HI or mild/moderate RI did not show an apparent impact on ribociclib PK. Using relevant data and methodology for EBC patients, this analysis informed the approved ribociclib label of no dose adjustment for EBC patients with concomitant use of a moderate CYP3A inhibitor, any degree of HI, or mild/moderate RI, and a reduced 200 mg dose for patients with concomitant use of a strong CYP3A inhibitor or severe RI.

In HR-positive HER2-negative metastatic breast cancer, no statistically significant negative association was observed in terms of survival and prognosis when switching from ribociclib to palbociclib after toxicity. Switching may be considered in selected patients during the treatment.

P2/3, N=36, Not yet recruiting, Eli Lilly & Co.