SHANGHAI, Oct. 23, 2023 — Luoxin Pharmaceutical Group Stock Co., Ltd. (Luoxin Pharmaceutical) has made a significant stride in the field of oncology with the presentation of Phase I clinical study data for its innovative anti-tumor drug, LX-039, at the 2023 ESMO Annual Congress in Madrid, Spain.
ESMO, a globally influential oncology conference, drew over 30,000 professionals from more than 150 countries and regions this year. The congress is a platform for discussing basic research, translational research, and the latest advancements in clinical studies, fostering exchanges in clinical diagnosis and treatment.
LX-039 is a groundbreaking selective estrogen receptor degrader (SERD) designed for oral administration. The Phase I study aimed to explore the drug’s safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) in postmenopausal patients with ER+ and HER2- advanced breast cancer who had previously failed endocrine therapy. The study was led by Professor Hu Xichun from Fudan University Shanghai Cancer Center.
Using a 3+3 design, the trial assessed safety and tolerability with daily doses ranging from 50 mg to 1200 mg, selecting two dosage groups for further expansion. PD study utilized [18F] Fluoroestradiol PET/CT imaging. All 44 participants had undergone multiple rounds of endocrine therapy, with 72.7% having received second-line therapy or higher. More than half had been treated with fulvestrant, a medication commonly used for hormone receptor-positive breast cancer. Additionally, over 50% had received advanced chemotherapy, and 40.9% had been treated with CDK4/6 inhibitors.
Notably, the study did not reach the maximum tolerated dose (MTD). Most adverse events were graded as mild to moderate (grade 1-2). The exposure to LX-039 increased with dose escalation, with no obvious accumulation after multiple doses. Inhibition of the ER pathway was observed in all subjects participating in the PD exploration. Four subjects achieved partial response, resulting in an objective response rate of 10.8% and a clinical benefit rate at 24 weeks of 40%. These promising findings indicate that LX-039 exhibits good tolerability and favorable PK/PD properties in ER+ and HER2- advanced breast cancer and shows preliminary anti-tumor activity. Consequently, a phase II study is in the planning stages.
About 75% of breast cancer cases are classified as ER+. This subtype of breast cancer relies on the estrogen signaling pathway for its growth and progression. The primary therapeutic approach for ER+ breast cancer involves inhibiting the estrogen signaling pathway through various methods. LX-039, an orally administered selective ER degrader (SERD), focuses on modulating the estrogen signaling pathway, offering unique therapeutic benefits compared to existing treatments. Importantly, its oral formulation enhances patient convenience and compliance, as it eliminates the need for injections. Currently, there are no domestically available oral drugs with a similar mechanism of action to LX-039 in the market.
The presentation of these Phase I study results at ESMO 2023 marks a significant step in the development of LX-039 and its potential as an effective treatment for advanced breast cancer.
Wang Y, Ayres K L, Goldman D A, et al. 18F-fluoroestradiol PET/CT measurement of estrogen receptor suppression during a phase I trial of the novel estrogen receptor-targeted therapeutic GDC-0810: using an imaging biomarker to guide drug dosage in subsequent trials[J]. Clinical Cancer Research, 2017, 23(12): 3053-3060.
Patel H K, Bihani T. Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment[J]. Pharmacology & therapeutics, 2018, 186: 1-24.