Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial

Lerociclib (GB491), a highly selective oral CDK4/6 inhibitor, has displayed anti-tumor activity and differentiated safety and tolerability profile in previous ph1/2 clinical trials. The LEONARDA-1, a randomized, double-blind, phase III study, was conducted to evaluate the efficacy and safety of lerociclib in HR+/HER2- locally advanced or metastatic breast cancer patients, who had relapsed or progressed on prior endocrine therapy. A total of 275 patients were randomized at 1:1 ratio to receive lerociclib (137 patients, 150 mg twice daily) or placebo (138 patients) plus fulvestrant. Progression-free survival (PFS) assessed by investigators was significantly improved in lerociclib arm versus placebo arm (11.07 vs 5.49 months; hazard ratio, 0.451, 95% CI: 0.311-0.656, P = 0.000016), meeting the pre-specified primary endpoint. The secondary endpoints included PFS assessed by Blinded Independent Central Review (BICR), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), safety and tolerability and pharmacokinetic profile. DOR is not reported, and OS data was immature at the data cut-off but unplanned ad hoc analysis is reported. These findings support lerociclib plus fulvestrant as a treatment option for patients with HR+/HER2- endocrine-resistant advanced breast cancer (ABC). (Funded by Genor Biopharma; LEONARDA-1 ClinicalTrials.gov identifier, NCT05054751.).

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Publication Details

Journal
Nature Communications
Published
2025-01-16
DOI
https://doi.org/10.1038/s41467-025-56096-2
Citations
6
Primary Topic
Advanced Breast Cancer Therapies
Type
article
Field-Weighted Citation Impact
9.11
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article

Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial

Xi Yan, Deyong Zhang, Changping Shan, Xinhong Wu et al.
6 citations
Nature Communications
Advanced Breast Cancer Therapies
9.11
article

Lerociclib plus fulvestrant in patients with HR+/HER2− locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy: LEONARDA-1 a phase III randomized trial

Xi Yan, Deyong Zhang, Changping Shan, Xinhong Wu, Fuming Qiu, Changlu Hu, Xinlan Liu, Xiaohua Zeng, Tao Sun, Tong Li, Yang Luo, Shusen Wang, Xiaojia Wang, Qingyuan Zhang, Zhendong Chen, Bing Zhao, Binghe Xu, Hongyan Jia, Zhongsheng Tong, Yumin Yao
article en
6 citations

Abstract

Lerociclib (GB491), a highly selective oral CDK4/6 inhibitor, has displayed anti-tumor activity and differentiated safety and tolerability profile in previous ph1/2 clinical trials. The LEONARDA-1, a randomized, double-blind, phase III study, was conducted to evaluate the efficacy and safety of lerociclib in HR+/HER2- locally advanced or metastatic breast cancer patients, who had relapsed or progressed on prior endocrine therapy. A total of 275 patients were randomized at 1:1 ratio to receive lerociclib (137 patients, 150 mg twice daily) or placebo (138 patients) plus fulvestrant. Progression-free survival (PFS) assessed by investigators was significantly improved in lerociclib arm versus placebo arm (11.07 vs 5.49 months; hazard ratio, 0.451, 95% CI: 0.311-0.656, P = 0.000016), meeting the pre-specified primary endpoint. The secondary endpoints included PFS assessed by Blinded Independent Central Review (BICR), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS), safety and tolerability and pharmacokinetic profile. DOR is not reported, and OS data was immature at the data cut-off but unplanned ad hoc analysis is reported. These findings support lerociclib plus fulvestrant as a treatment option for patients with HR+/HER2- endocrine-resistant advanced breast cancer (ABC). (Funded by Genor Biopharma; LEONARDA-1 ClinicalTrials.gov identifier, NCT05054751.).

Nature CommunicationsVol. 16(1)
Xinjiang Medical University (CN), Harbin Medical University (CN), Sun Yat-sen University (CN), Chongqing University (CN), Shanxi Medical University (CN), Anhui Medical University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Sichuan University (CN), Tianjin Medical University Cancer Institute and Hospital (CN), National Cancer Center (US), West China Hospital of Sichuan University (CN), Zhejiang Cancer Hospital (CN), Tumor Hospital of Xinjiang Medical University (CN), Third Affiliated Hospital of Harbin Medical University (CN), First Hospital of Shanxi Medical University (CN), Ningxia Medical University (CN), Anhui Provincial Hospital (CN), Ningxia Medical University General Hospital (CN), Cancer Hospital of Chinese Academy of Medical Sciences (CN), Sun Yat-sen University Cancer Center (CN), Second Affiliated Hospital of Anhui Medical University (CN), Chongqing Cancer Hospital (CN), Second Affiliated Hospital of Zhejiang University (CN), Liaocheng People's Hospital (CN), Hubei Cancer Hospital (CN), Liaoning Cancer Hospital & Institute (CN), Affiliated Hospital of Jining Medical University (CN), University of Chinese Academy of Sciences (CN), China Medical University (CN)
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Openalex Percentile: Top 2%
Advanced Breast Cancer Therapies
9.11
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