American Society of Clinical Oncology (ASCO) Annual Meeting 2023 was successfully held in Chicago, US from June 2 to June 6. ASCO 2023 brought together experts and scholars from the global oncology community to share the latest research progress and discuss the future exploration direction.
The LEONARDA-1 data has been posted on Sunday, June 4 CDT in Hall D2 during ASCO’s Metastatic Breast Cancer session with the abstract title as: Phase III randomized study of lerociclib plus fulvestrant in patients with HR+/HER2- locally advanced or metastatic breast cancer that has progressed on prior endocrine therapy. Abstract Number: 1017, Poster Bd#: 238.
The 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 interpreted the research results in detail through video, analyzed the current difficulties in the treatment of HR+/HER- breast cancer, and commented on the limitations of the current treatment of CDK4/6 inhibitors. It is expected that Lerociclib (GB491) will become the preferred CDK4/6 inhibitor.
“Lerociclib provides patients with breast cancer efficacious treatment with potential best-in-class safety profile.” Prof. Binghe XU said.
Dr. GUO Feng, Chairman of the Board and Chief Executive Officer, Genor Biopharma, said: “Results from the LEONARDA-1 trial indicated significantly greater progression-free survival with lerociclib/fulvestrant versus fulvestrant/placebo. We expect to improve the quality of life of patients with unmet medical needs through this effective CDK4/6 inhibitor with a significant safety advantage.”
Scan the following QR code to learn the full content of Prof. Binghe XU's video:
Based on the efficacy and safety data presented in the LEONARDA-1, Lerociclib (GB491) is expected to be a more reliable clinical option for patients with HR+/HER2- advanced breast cancer. Lerociclib (GB491) could become a preferred option among CDK4/6 inhibitors for patients with suboptimal recovery of myelosuppression after chemotherapy and suboptimal gastrointestinal / hepatic function or patients with poor tolerability.
- LEONARDA-1 study met the primary endpoint, demonstrating the superiority of Lerociclib plus Fulvestrant versus Placebo plus fulevestrant.
- The risk of investigator-assessed disease progression or death was significantly reduced by about 55%. The median PFS was 11.07 months in the Lerociclib group, and 5.49 months in the placebo group. Blind independent imaging assessment (BICR) results were consistent with the investigators' assessment, with an approximately 65% reduction in the risk of disease progression or death, with PFS of 11.93 months in the Lerociclib group versus 5.75 months in the placebo group.
- Efficacy in all patient subgroups were highly consistent with overall efficacy. In the clinically common subgroup with poor prognosis, the risk of disease progression or death was significantly reduced with Lerociclib (GB491). Such as:
- Patients with liver metastasis (HR 0.487), primary endocrine resistant patients (HR 0.374), patients treated with first-line chemotherapy agents at stages of tumor recurrence and metastasis (HR 0.286), patients with 4 or more metastatic organs (HR 0.326); the use of Lerociclib (GB491) can significantly increase progression-free survival (PFS).
- In premenopausal/perimenopausal patients (HR 0.471), Lerociclib (GB491) also achieved significant clinical benefit.
- Lerociclib also demonstrated a very favorable safety and tolerability profile when given as continuously daily dosing. Lerociclib (GB491) has mild myelosuppression. Grade 4 neutropenia was reported in only 5%, diarrhea was reported in only 19.4%, no grade III or above diarrhea reported. Lerociclib (GB491) did not increase the risk of liver and cardiotoxicity compared with placebo. No venous thromboembolic events (VTE) reported. Incidence of skin rash was low and similar, both being around 4%. No hair loss and other adverse events reported. The use of Lerociclib (GB491) is easier to manage clinically, better tolerated by patients and significantly improves patients' quality of life.
The latest research data of LEONARDA-1 were selected by 2023 ASCO for the ASCO Daily Release, which was published in the ASCO Daily News Column on its website on May 25 (EST).
Based on the results of LEONARDA-1, NMPA has officially accepted the new drug application for GB491 (Lerociclib) in combination with Fluvestran as the treatment of HR+/HER2- locally advanced or metastatic breast cancer patients with disease progression following previous endocrine therapy on March 28, 2023.
Background:
Lerociclib is a novel CDK4 and 6 inhibitor, it is highly selected and potent for CDK4 and CDK6, but only moderate inhibition on CDK9.
Lerociclib 150mg twice a day, continuously daily dosing, demonstrated anti-tumor activity and a differentiated safety and tolerability profile in previous clinical trials.
Herein, we conducted this phase 3 LEONARDA-1 study to evaluate the efficacy and safety of Lerociclib plus fulvestrant versus placebo plus fulvestrant in advanced breast cancer.
Patients with HR positive, HER2 negative locally advanced or metastatic breast cancer who have progressed on prior endocrine therapy were randomized at a 1 to 1 ratio.
Stratification factors were presence of visceral metastasis, menopausal status, and previous endocrine therapy failure lines.
Baseline Characteristics:
At the data cut-off date, 275 patients were randomized, 137 patients received Lerociclib plus fulvestrant, and 138 patients received placebo plus fulvestrant.
The patients’ baseline characteristics were well balanced. About 25% of patients were primary resistance to prior endocrine therapy, 30% received one prior line of chemotherapy in metastasis setting, 43% were pre- or peri-menopausal, and over 60% had visceral metastasis.
Efficacy Results:
The study met the primary end point.
Investigator-assessed PFS was significantly improved. The Hazard ratio was 0.451, median PFS was around 11 months in the Lerociclib group, and 5.5 months in the placebo group.
The PFS result, based on independent review committee assessment, was consistent with the primary analysis. The Hazard ratio was 0.353.
PFS Subgroup analysis:
PFS in all pre-specified subgroups favored the lerociclib group. The improvement in PFS with Lerociclib was observed in patients with poor prognosis, such as patients with primary endocrine resistant, pre- or peri-menopausal patients, patients with liver metastasis, and patients received one line of chemotherapy for metastatic disease.
Safety Summary and Study Conclusion:
The occurrence of grade 3 and 4 adverse events was more frequent in lerociclib group than placebo group.
However, the incidence of serious adverse events, AE leading to treatment discontinuation, and fatal adverse events were lower or comparable between the groups.
The most common adverse events for lerociclib group versus placebo group were neutropenia, leucopenia, anemia, thrombocytopenia and diarrhea. Grade 4 neutropenia was reported in only 5% patients in lerociclib group, no febrile neutropenia reported. The incidence of abnormal liver function was similar between two groups, and the incidence of skin rash was low and similar, both being around 4%. There is no Grade 3 or 4 diarrhea reported, and no VTE reported.
About GB491 (Lerociclib)
GB491 (Lerociclib) is a highly selective oral CDK4/6 inhibitor for the treatment of breast cancer. The company in-licensed exclusive rights of GB491 (Lerociclib) from G1 Therapeutics, Inc. (Nasdaq: GTHX) in certain APAC countries excluding Japan in June 2020.
