The latest research data of Lerociclib(GB491) was selected by ASCO Daily News Column, Genor Biopharma’s CDK4/6 inhibitor recognized at globe

29 May, 2023

The latest research data of Lerociclib(GB491) was selected by ASCO Daily News Column, Genor Biopharma's CDK4/6 inhibitor recognized at globe

Shanghai, China, May 29, 2023 - Genor Biopharma (Stock code: 6998.HK) announced that 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). Entitled "Lerociclib/Fulvestrant May Reduce Risk of Disease Progression in Advanced HR-Positive/HER2-Negative Breast Cancer", the article presents data from the Phase III clinical study of LEONARDA-1, citing the views of 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.

Please find the full ASCO Daily News article as below:

• LEONARDA-1 data indicate significantly greater progression-free survival with lerociclib/fulvestrant versus fulvestrant/placebo (HR 0.451; P < .001) in patients with HR-positive/HER2-negative advanced breast cancer.

• Most patients had at least 1 prior line of chemotherapy containing taxanes, anthracycline, or cyclophosphamide; 29.1% had received first-line chemotherapy in the recurrent and metastatic stage.

• In the ITT population, the ORR was 23.4% in the lerociclib/fulvestrant group versus 8.7% in the fulvestrant/placebo group.

• Incident grade 4 neutropenia was low, and no cases of febrile neutropenia or grade 3/4 diarrhea were observed.

Results from the LEONARDA-1 trial indicated significantly greater progression-free survival and overall response rate (ORR) with lerociclib/fulvestrant versus fulvestrant/placebo.

In addition, promising efficacy was observed in patients who typically have a poor prognosis. Among the patients who had received first-line chemotherapy during the recurrence and metastasis stage, the hazard ratio [HR] reached 0.286; among patients with primary endocrine resistance, the HR was 0.374; in premenopausal/perimenopausal patients with primary endocrine resistance, it was 0.496; and in patients with liver metastases, it was 0.487.

LEONARDA-1 is the first phase III randomized controlled trial for lerociclib in HR+/HER2- recurrent or metastatic breast cancer patients who have progressed on prior endocrine therapy. The trial, which was conducted in China, could help fill gaps in knowledge about how CDK4/6 inhibitors such as lerociclib can be leveraged to improve both survival and safety outcomes in patients with breast cancer for whom endocrine therapy failed.

The LEONARDA-1 data will be 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.

Not Just Clinical Efficacy, but Safety

Treatment of HR-positive/HER2-negative breast cancers is complicated by the high degree of variation among HR-positive tumors in terms of biologic behavior and responsiveness to endocrine therapy and chemotherapy.¹ Further compounding treatment goals is the fact that patients with HR-positive/HER-negative breast tumors demonstrate an elevated risk for disease recurrence, even after a decade or longer.

Given the pivotal role of endocrine suppression in garnering desirable outcomes in these patients, endocrine therapy has become the cornerstone of HR-positive/HER2-negative breast cancer treatment.^1,2

Numerous trials have established the efficacy of the endocrine receptor degrader fulvestrant as a critical therapeutic for this population.^2,3

Nevertheless, endocrine resistance remains a major problem and underscores the importance of continuing to refine the treatment landscape beyond endocrine therapies alone. For instance, data from trials of fulvestrant in combination with CDK4/6 inhibitors suggest a survival benefit and potential reversal of endocrine resistance.^2,3 Unfortunately, Dr. Xu said, CDK4/6 inhibitors are commonly associated with adverse reactions such as hematologic toxicity, gastrointestinal toxicity, abnormal liver function, venous thromboembolism, and skin adverse reactions. These have limited the clinical application of CDK4/6 inhibitors in this population of patients with breast cancer.

"Based on the current unmet medical needs, we hope to develop a CDK4/6 inhibitor that is not only efficacious but also has significant safety advantages to improve patients' quality of life, which is essential" for patients with breast cancer, he added.

The only CDK4/6 inhibitors currently approved by the U.S. Food and Drug Administration for the treatment of HR-positive/HER2-negative advanced breast cancer are abemaciclib, palbociclib, and ribociclib. But favorable results from LEONARDA-1 might inform future phase 3 trials (in US) and help expand this list to eventually include lerociclib. Lerociclib is currently under investigation in phase 1 and 2 clinical trials (NCT02983071and NCT05085002) of HR-positive/HER2-negative advanced breast cancer in the United States and international locations.

A More Tolerable Treatment?

LEONARDA-1 is a phase 3 trial comparing lerociclib/fulvestrant versus fulvestrant/placebo (control group). Most patients enrolled (92.7%) had at least 1 prior line of chemotherapy containing taxanes (78.2%), anthracycline (70.9%), or cyclophosphamide (68.4%); 29.1% had received first-line chemotherapy in the recurrent and metastatic stage. Prior endocrine therapy had failed in all participants, and 25.5% of enrolled patients had primary resistance to endocrine therapy. Investigators also enrolled patients who typically do not fare well with this form of breast cancer, such as premenopausal and perimenopausal women, men, and patients with multiple visceral metastasis.

As of December 2022, data indicate significantly greater progression-free survival with the study group versus control (HR 0.451; P < .001). Similar progression-free survival improvements were observed among high-risk populations, including patients with primary endocrine resistance, premenopausal/perimenopausal women, and patients with visceral metastases.

Additionally, the objective response rate (ORR) was significantly higher in the study group. In the intention-to-treat population, the ORR was 23.4% in the lerociclib/fulvestrant group versus 8.7% in the control group. For patients with measurable disease at baseline, the ORR was 26.9% in the lerociclib/fulvestrant group versus 9.9% in the control group.

Regarding toxicities, incident grade 4 neutropenia was low (5.1%), and no cases of febrile neutropenia or grade 3/4 diarrhea were observed. No thromboembolic events were reported in this study. Incidence of abnormal liver function was similar between groups, and incidence of skin rash was low and similar, with both groups being around 4%.

"Lerociclib provides [patients with] breast cancer efficacious treatment with potential best-in-class safety profile so that it may improve patient quality of life while dealing with this desperate disease," Dr. Xu said.

Dr. Xu expects lerociclib to become an important supplement to the existing treatment landscape for HR-positive/HER2-negative advanced breast cancer.

"It 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," he added.

These findings are consistent with those from a recent phase 1/2 study (conducted in US) of patients with HR-positive/HER2-negative advanced breast cancer that found lerociclib/fulvestrant was associated with low rates of grade 4 neutropenia, gastrointestinal toxicity, fatigue, stomatitis, and alopecia.4 Additionally, the efficacy data were consistent with that of fulvestrant combined with marketed CDK4/6 inhibitors.4 LEONARDA-1 could help build upon these findings through its larger sample (275 patients) and randomization with placebo controls.

Dr. Xu and his colleagues have completed the primary analyses from LEONARDA-1 and will next consider ad hoc analyses with emerging data, such as data on overall survival outcomes and other subgroup analyses for certain populations.

"The overall survival data [from LEONARDA-1] is not yet mature, and we hope we will be able to confirm the survival trend seen with the current data with longer follow-up," Dr. Xu added.

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.

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