Editor’s Note: Breast cancer remains the most common malignancy among women, with hormone receptor–positive/HER2-negative (HR+/HER2–) cases accounting for approximately 70% of all diagnoses. For patients with advanced disease, first-line therapy typically combines endocrine treatment with a CDK4/6 inhibitor (CDK4/6i). On May 29, 2025, China reached a new milestone in breast cancer therapy — the novel CDK4/6 inhibitor Lerociclib (brand name: Rujianing®) received NMPA approval for use in adult HR+/HER2– metastatic breast cancer (MBC), both:- in combination with an aromatase inhibitor (AI) as initial endocrine therapy, and
- in combination with fulvestrant for patients with disease progression following prior endocrine therapy.
This approval signifies that China’s HR+/HER2– breast cancer treatment has entered a new era. Now, just over three months later, the first clinical prescriptions for Lerociclib in combination with aromatase inhibitors have been officially issued across major hospitals in Shanghai, Zhejiang, Beijing, and Heilongjiang, marking nationwide clinical accessibility and bringing this advanced therapy to a broader population of patients.
The First Lerociclib Prescription: A New Frontier for HR+/HER2– Advanced Breast Cancer
On May 29, 2025, the novel CDK4/6 inhibitor Lerociclib (Rujianing®, by Genor Biopharma) received NMPA approval for combination with aromatase inhibitors as first-line endocrine therapy for HR+/HER2– locally advanced or metastatic breast cancer.
Developed jointly by Genor Biopharma (China) and G1 Therapeutics (U.S.), Lerociclib was designed to address key clinical limitations of earlier CDK4/6 inhibitors.
The approval was based on the outstanding efficacy demonstrated in the LEONARDA-2 Phase III study: Compared to placebo plus letrozole, the Lerociclib + letrozole regimen significantly prolonged median progression-free survival (mPFS) — not reached versus 16.56 months — and reduced the risk of disease progression or death by 54% (HR = 0.464).
The first Lerociclib prescriptions, issued by investigators from the LEONARDA-2 study at major hospitals nationwide, mark a transformative moment in precision therapy for Chinese patients with HR+/HER2– advanced breast cancer.
Global Quality, Structural Innovation: How Lerociclib Achieves “Precision Targeting with High Efficacy and Low Toxicity”
Lerociclib’s success stems from its dual innovation in molecular structure and pharmacologic mechanism:
1. Unique “Tricyclic & Spirocyclic” Scaffold Design Lerociclib is the first CDK4/6 inhibitor to incorporate this highly differentiated structure, enhancing target affinity and minimizing off-target effects, which leads to improved precision and tolerability.
2. Optimized Pharmacokinetics and Pharmacodynamics (PK/PD) The innovative design enables lighter bone marrow suppression, significantly reducing severe neutropenia and allowing continuous daily dosing — ensuring sustained target inhibition and prolonged antitumor activity.
3. High Selectivity & Deep Tumor Penetration Lerociclib demonstrates highly selective CDK4 inhibition with a lower IC50 than other CDK4/6 inhibitors. It has a substantially larger apparent distribution volume, leading to broad tissue diffusion and deep tumor enrichment:
- Tumor exposure is 18× higher than plasma levels.
- At 24 hours post-dose, when plasma concentrations are minimal, tumor concentrations are over 100× higher.
- At 48 hours, tumor concentrations remain as high as ~65 ng/mL, while plasma levels are nearly undetectable. This superior intratumoral permeability ensures durable, localized inhibition and a robust anticancer effect.
Global Quality, Chinese Evidence: The Only Originator CDK4/6i Approved Based on All-Chinese Trials
Lerociclib’s efficacy and safety are validated by two pivotal Phase III studies—LEONARDA-1 and LEONARDA-2—both conducted entirely in Chinese populations.
LEONARDA-1: Second-Line Therapy Validation (Nature Communications, 2025)
Led by Professor Binghe Xu (National Cancer Center, CAMS), this randomized, double-blind, Phase III trial enrolled 275 Chinese patients with HR+/HER2– advanced or metastatic breast cancer who had progressed after prior endocrine therapy.
Results:
- mPFS: 11.07 vs 5.49 months (HR 0.451; P < 0.001)
- Risk of progression or death reduced by 55%.
- In difficult-to-treat subgroups — patients with >3 metastatic sites or prior chemotherapy — Lerociclib + fulvestrant demonstrated higher clinical benefit rates.
LEONARDA-2: First-Line Therapy Success (ASCO 2024)
Led by Professor Xichun Hu (Fudan University Shanghai Cancer Center), this Phase III, multicenter, randomized, double-blind study enrolled 279 untreated Chinese HR+/HER2– MBC patients.
Results:
- mPFS: Not reached vs 16.56 months (HR 0.464; 95% CI 0.293–0.733; P = 0.0004)
- 54% risk reduction in progression or death.
Safety Profile: Well-Tolerated and Suitable for Long-Term Use
Both trials confirmed that Lerociclib’s main adverse events were hematologic, but discontinuation rates due to AEs remained extremely low. Lerociclib did not increase risks of hepatotoxicity, QT prolongation, or VTE, and requires no special safety monitoring — ideal for long-term maintenance therapy.
A New Standard for HR+/HER2– Advanced Breast Cancer: “High Selectivity, Deep Penetration, High Benefit, Low Disruption”
As the world’s first CDK4/6 inhibitor with a “tricyclic + spirocyclic” structure, Lerociclib redefines the standards of endocrine combination therapy for HR+/HER2– advanced breast cancer. Its approval and first clinical prescriptions represent a new era of high-efficiency, low-toxicity therapy, offering patients longer survival and better quality of life.
Lerociclib (Rujianing®) stands as a landmark achievement in global oncology — a product of international collaboration, Chinese clinical excellence, and the growing global influence of Chinese medical innovation.
