Genor Biopharma (Stock code: 6998.HK) announced that the research data of Lerociclib (GB491, a highly selective oral CDK4/6 inhibitor) Phase III clinical trial has been published in <Nature Communications>, titled as “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”, on January 16, 2025.
The LEONARDA-1 (ClinicalTrials.gov identifier, NCT05054751), a randomized, double-blind, phase III study led by lead author Prof. Binghe Xu, MD, PhD, the academician of the Chinese Academy of Engineering, the Head of Medical Oncology at Cancer Hospital affiliated with Chinese Academy of Medical Sciences. The clinical trial 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 addition of lerociclib to fulvestrant improved PFS across all prespecified patient subgroups, including patients with poor prognosis, such as primary ET resistance (HR: 0.374; 95% CI: 0.182–0.769), liver metastasis (HR: 0.487; 95% CI: 0.297–0.796), ≥4 metastatic sites (HR: 0.326; 95% CI: 0.160–0.665), received one line of chemotherapy for recurrent/metastatic disease (HR: 0.286; 95% CI: 0.138–0.593), and pre/perimenopausal women or men (HR: 0.471; 95% CI: 0.258–0.860).
As of the data cut-off, OS results were not yet mature, with 9 deaths (6.6%) in the lerociclib arm and 13 deaths (9.4%) in the placebo arm (HR: 0.630, 95% CI: 0.267–1.484; median OS: not reached in both arms). An ad hoc analysis of OS was conducted (DCO: March 30, 2024) with a median follow-up duration of 23 months, at which time there were 32 and 43 deaths in the lerociclib arm and placebo arm, respectively. Median OS was not reached in either arm and the HR was 0.649 (95% CI: 0.410, 1.028).
The safety profile of lerociclib plus fulvestrant was very favorable and the AEs were well managed and only one patient (0.7%) discontinued treatment due to AE. The most common grade 3 or 4 events associated with lerociclib treatment were hematological toxicities (primarily neutropenia and leukopenia). The incidence of grade 3 or 4 neutropenia of lerociclib was 46.7% with a low incidence of grade 4 (5.1%), and no febrile neutropenia was reported. In addition, gastrointestinal toxicity including diarrhea, nausea and vomiting, a common adverse effect of abemaciclib and ribociclib, were observed in less than 20% of the patients treated with lerociclib and no grade 3 or 4 diarrhea was reported. Moreover, no VTE were reported; few cases of QTc prolongation were reported in each treatment arm; and the incidence of skin rash was low and similar between the lerociclib and placebo arms, both being around 4%. Finally, lerociclib did not pose an additional risk for hepatotoxicity.
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 new drug application for GB491 (Lerociclib) in combination with Fulvestrant as the treatment of HR+/HER2- locally advanced or metastatic breast cancer patients with disease progression following previous endocrine therapy has been accepted by the China National Medical Products Administration (NMPA) on March 28, 2023, and has successfully completed clinical on-site inspection and the drug testing at the National Institutes for Food and Drug Control.
In addition, the China National Medical Products Administration (NMPA) has officially accepted the new drug application for GB491 (Lerociclib) combined with Letrozole for the treatment of HR-positive, HER2-negative patients with advanced breast cancer who have not previously undergone systemic antitumor therapy on March 13, 2024.
About GB491 (Lerociclib)
GB491 (Lerociclib) is a highly selective oral CDK4/6 inhibitor for the treatment of breast cancer. It was developed by Genor Biopharma and G1 Therapeutics (Pharmacosmos). The company in-licensed exclusive rights of GB491 (Lerociclib) from G1 Therapeutics (Pharmacosmos), in certain APAC countries excluding Japan in June 2020.
About Nature Communications
Nature Communications is an open access, multidisciplinary journal dedicated to publishing high-quality research in all areas of the biological, physical, chemical and Earth sciences. Papers published by the journal represent important advances of significance to specialists within each field. The scope of the journal reflects Nature Publishing Group's core strength in the natural sciences, and includes areas in which Nature research journals serve to publish the most outstanding community-focused research papers.
