P1, N=24, Not yet recruiting, Capital Medical University

P2, N=19, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Apr 2026 --> Nov 2025

P2, N=60, Recruiting, University of Texas Southwestern Medical Center | Trial primary completion date: Apr 2026 --> Apr 2027

P3, N=120, Recruiting, Pharmacosmos A/S | Not yet recruiting --> Recruiting | Initiation date: Mar 2026 --> Jun 2026

A transcriptional signature associated with SARM sensitivity was identified, primarily driven by proliferation-related processes, consistent with a significant decrease in S-phase cell cycle proteins upon treatment in EP0062-sensitive models. In some EP0062-resistant tumors, the combination with palbociclib enhanced the antitumor effect of EP0062, suggesting a potential strategy for metastatic patients with acquired ET resistance.

We retrospectively analyzed 332 patients with hormone receptor-positive/HER2-negative metastatic breast cancer who received first-line ribociclib or palbociclib plus endocrine therapy between 2018 and 2023. These findings suggest a potential association between BMI and clinical outcomes in this treatment setting. Prospective studies that integrate body composition and pharmacokinetics are required for validation.

P=N/A, N=750, Completed, Novartis Pharmaceuticals

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, such as abemaciclib, ribociclib, and palbociclib, are used in combination with ET as a standard of care first-line option in HR+, HER2- advanced disease to improve survival outcomes...Abemaciclib has also been shown to be effective when combined with a variety of ET options, including aromatase inhibitors, tamoxifen, fulvestrant, imlunestrant, or as monotherapy, and has shown efficacy regardless of prior CDK4/6 inhibitor exposure, ESR1 or PI3K pathway mutational status, menopausal status, and in both endocrine-sensitive and endocrine-resistant breast cancer. Importantly, the safety profile of abemaciclib has been consistent across trials and allows the administration of the drug over long periods of time when needed, particularly if dose-reduction strategies are employed. Together, the data summarized in this publication help inform clinical decision making regarding the role of abemaciclib in the treatment of patients with both early and metastatic HR+, HER2- breast cancer.

In EBC, no OS benefit was observed, and toxicity was increased, underscoring the need for individualized risk-benefit assessment. Longer follow-up is warranted to clarify survival outcomes.

ESR1 and RB1 alterations were significantly more frequent post-CDK4/6i. Patients with CDK4/6i + ET-R mutations prior to CDK4/6i treatment had significantly worse outcomes in terms of time on CDK4/6i and OS, suggesting that this resistance signature could prove useful in better refining personalized treatment selection in future clinical practice, though further exploration is needed.

P1, N=45, Recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

P=N/A, N=200, Recruiting, Region Jönköping County | Not yet recruiting --> Recruiting