Palbociclib Monotherapy Demonstrates Modest Clinical Activity Among Patients With Locally Advanced or Metastatic Chordoma

According to final results from the NCT PMO-1601 trial, palbociclib monotherapy demonstrated modest clinical activity among patients with locally advanced or metastatic chordoma. 

“To date, there are no approved drugs for the treatment of locally advanced or metastatic chordoma,” stated Maria-Veronica Teleanu, MD, National Center for Tumor Diseases, Heidelberg, Germany, and coauthors. “Previous data showed that palbociclib reduced cell viability and proliferation in CDKN2A-deficient chordoma cell lines.”

In this open-label, single-arm study, researchers enrolled 28 patients with locally advanced or metastatic chordoma with p16 or CDKN2A loss and CDK4/6 and RB1 expression. Patients received 125 mg of palbociclib once daily on days 1 to 21 in a 28-day cycle until disease progression or unacceptable toxicity. The primary end point was disease control rate. Key secondary end points included objective response, progression-free survival (PFS), overall survival (OS), and safety. 

At a median follow-up of 28 months, the disease control rate was 39%. Eleven patients achieved stable disease, and no objective responses were observed. The median PFS was 5.6 months, and the median OS was 24.6 months. Treatment-related adverse events occurred in 96.4% of patients. Grade ≥3 treatment-related adverse events occurred in 39.2% of patients. The most frequently observed grade ≥3 treatment-related adverse event was neutropenia occurring in 28.5% of patients. Biomarker analyses revealed that there was no correlation between immunohistochemical response phenotype and outcome. Additional clinically actionable alterations affecting PIK3CA, PTEN, MTAP, or MET gene, and druggable pathways were identified via transcriptomic analysis. 

“Although antitumor activity was modest, the trial met its primary end point,” concluded Dr Teleanu et al. “Molecularly tailored combination therapies should be considered in the future to improve efficacy.”

Source: 

Teleanu MV, Heilig CE, Pirmann S, et al. CDK4/6 inhibition in advanced chordoma: Final results of the NCT PMO-1601 trial. ESMO Open. Published online: July 7, 2025. doi: 10.1016/j.esmoop.2025.105498