From October 20 to 24, the 2023 ESMO Congress was held in Madrid, Spain. LX-039, an innovative anti-tumor drug developed by Luoxin Pharmaceuticals Group Stock Co., Ltd. (Luoxin Pharmaceutical), was selected for poster presentation at the 2023 ESMO Annual Congress. ESMO is one of the most influential oncology conferences globally, attracting over 30,000 professionals every year from more than 150 countries and regions.

The Congress covers basic research, translational research, and the latest advancements in clinical studies, providing an exchange platform in clinical diagnosis, treatment, and academic discussions. LX-039 is an innovative selective estrogen receptor degrader (SERD) for oral administration. The aims of the dose escalation and expansion phase I study was to explore the safety, tolerability, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) profiles of LX-039 in postmenopausal patients with ER+ and HER2- advanced breast cancer who have failed endocrine therapy.

The study was led by Professor Hu Xichun from Fudan University Shanghai Cancer Center. In a 3+3 design, the trial evaluated the safety and tolerability from a daily dose of 50 mg to 1200 mg, with two dose groups selected for expansion. [18F] Fluoroestradiol PET/CT imaging was used for PD study.

All 44 enrolled subjects had previously undergone multiple lines of endocrine therapy. Specifically, 72.7% had received second-line therapy or higher. More than half had been treated with fulvestrant, a medication commonly used for hormone receptor-positive breast cancer.

Also, over 50% had received advanced chemotherapy, and 40.9% had been treated with CDK4/6 inhibitors. Maximum tolerated dose (MTD) was not reached in this study. Most adverse events are graded as mild to moderate (grade 1-2).

The exposure of LX-039 increased along with the dose escalation, and no obvious accumulation after multiple doses. Inhibition of the ER pathway is observed in all subjects participating in the PD exploration. Four subjects achieved partial response, with an objective response rate of 10.8% and a clinical benefit rate at 24 weeks of 40%.

LX-039, an orally administered selective ER degrader (SERD") developed by Louxin Pharmaceutical, specifically focuses on modulating the estrogen signaling pathway. It antagonizes ER actions and promotes its ubiquitination and degradation within breast cancer cells, downregulating ER expression. LX-039 offers unique therapeutic benefits compared to selective ER modulators and aromatase inhibitors.

Additionally, its oral formulation enhances patient convenience and compliance, as it eliminates the need for injections. There are currently no domestically available oral drugs with a similar mechanism of action to LX-039 in the market.