A randomized controlled trial of CDK7 inhibitor samuraciclib plus fulvestrant in advanced HR+/HER2− breast cancer
Abstract
Resistance to CDK4/6 inhibitors remains a major challenge in HR+/HER2− metastatic breast cancer. Samuraciclib is an oral selective CDK7 inhibitor that may overcome resistance to CDK4/6 inhibitors, targeting transcriptional programs sustaining tumor growth. This study presents a 3-arm randomized comparison of samuraciclib 360 mg plus fulvestrant, samuraciclib 240 mg plus fulvestrant and fulvestrant alone in females with advanced HR+/HER2− breast cancer previously treated with a CDK4/6 inhibitor (NCT05963984). 59 patients were randomized and stratified by TP53 mutation and liver metastases status. 20, 19, and 20 patients were allocated to the samuraciclib 360 mg, 240 mg or fulvestrant arms respectively. For samuraciclib 360 mg plus fulvestrant and samuraciclib 240 mg plus fulvestrant compared with fulvestrant monotherapy, the primary endpoint of clinical benefit rate was 60.0%, 63.2% and 40.0%, respectively. Activity was enhanced in the selected secondary analysis populations of participants with no detectable TP53 mutations ( TP53 wild-type), participants with no baseline liver metastases and participants with prior CDK4/6 inhibitor duration of ≥12 months. Adverse events were predominantly gastrointestinal toxicities, manageable with prophylaxis. These results support CDK7 inhibition with samuraciclib plus fulvestrant as a potential second line strategy in HR+/HER2- breast cancer and provide a rationale for a biomarker enriched ( TP5 3 wild-type tumors) clinical evaluation.
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BibTeX
@article{pernas2026randomized,
title = {{A randomized controlled trial of CDK7 inhibitor samuraciclib plus fulvestrant in advanced HR+/HER2− breast cancer}},
author = {Sonia Pernas and Cengiz Karacin and Carlos Gonzalez-Nuñez and Sercan Aksoy and Meritxell Bellet Ezquerra and Nuri Karadurmus and Ozan Yazici and Maysa Abu-Khalaf and Begoña Bermejo de lasHeras and Marta Gonzalez Cordero and Mahmut Gumus and Carmen Hinojo and Rebeca Lozano Mejorada and Emmanuel de la Mora Jimenez and Carlos Zuloaga Fernandez del Valle and Cagatay Arslan and Shweta Kurian and María Martínez García and Daniel Motola-Kuba and Javier Pascual and Timothy Pluard and Gyongyver Szentmartoni and Glen Clack and Ash Bahl and Stuart McIntosh and Raoul Charles Coombes},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78309-y},
url = {https://www.nature.com/articles/s41467-026-78309-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A randomized controlled trial of CDK7 inhibitor samuraciclib plus fulvestrant in advanced HR+/HER2− breast cancer
AU - Sonia Pernas
AU - Cengiz Karacin
AU - Carlos Gonzalez-Nuñez
AU - Sercan Aksoy
AU - Meritxell Bellet Ezquerra
AU - Nuri Karadurmus
AU - Ozan Yazici
AU - Maysa Abu-Khalaf
AU - Begoña Bermejo de lasHeras
AU - Marta Gonzalez Cordero
AU - Mahmut Gumus
AU - Carmen Hinojo
AU - Rebeca Lozano Mejorada
AU - Emmanuel de la Mora Jimenez
AU - Carlos Zuloaga Fernandez del Valle
AU - Cagatay Arslan
AU - Shweta Kurian
AU - María Martínez García
AU - Daniel Motola-Kuba
AU - Javier Pascual
AU - Timothy Pluard
AU - Gyongyver Szentmartoni
AU - Glen Clack
AU - Ash Bahl
AU - Stuart McIntosh
AU - Raoul Charles Coombes
PY - 2026
DA - 2026/10/05
JO - Nature Communications
DO - 10.1038/s41467-026-78309-y
UR - https://www.nature.com/articles/s41467-026-78309-y
AB - Resistance to CDK4/6 inhibitors remains a major challenge in HR+/HER2− metastatic breast cancer. Samuraciclib is an oral selective CDK7 inhibitor that may overcome resistance to CDK4/6 inhibitors, targeting transcriptional programs sustaining tumor growth. This study presents a 3-arm randomized comparison of samuraciclib 360 mg plus fulvestrant, samuraciclib 240 mg plus fulvestrant and fulvestrant alone in females with advanced HR+/HER2− breast cancer previously treated with a CDK4/6 inhibitor (NCT05963984). 59 patients were randomized and stratified by TP53 mutation and liver metastases status. 20, 19, and 20 patients were allocated to the samuraciclib 360 mg, 240 mg or fulvestrant arms respectively. For samuraciclib 360 mg plus fulvestrant and samuraciclib 240 mg plus fulvestrant compared with fulvestrant monotherapy, the primary endpoint of clinical benefit rate was 60.0%, 63.2% and 40.0%, respectively. Activity was enhanced in the selected secondary analysis populations of participants with no detectable TP53 mutations ( TP53 wild-type), participants with no baseline liver metastases and participants with prior CDK4/6 inhibitor duration of ≥12 months. Adverse events were predominantly gastrointestinal toxicities, manageable with prophylaxis. These results support CDK7 inhibition with samuraciclib plus fulvestrant as a potential second line strategy in HR+/HER2- breast cancer and provide a rationale for a biomarker enriched ( TP5 3 wild-type tumors) clinical evaluation.
SN - 2041-1723
ER -