Affiliation:
1. Department of Breast Medicine Hunan Cancer Center Changsha Hunan China
2. Department of Breast Oncology, Sun Yat‐Sen Memorial Hospital Sun Yat‐Sen University Second Affiliated Hospital of Sun Yat‐Sen University Guangzhou China
3. Department of Medical Oncology Fudan Shanghai University Cancer Center Shanghai China
4. Clinical Research Center, Shanghai Hansoh Biomedical Co., Ltd. Shanghai China
Abstract
AbstractBackgroundApproximately 40% of patients with hormone receptor (HR)‐positive and human epidermal growth factor receptor 2 (HER2)‐negative advanced breast cancer (ABC) exhibit PIK3CA mutations.AimsThis study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of HS‐10352, a selective PI3Kα inhibitor, in this patient population.Materials and MethodsConducted as a phase 1 dose‐escalation trial, HS‐10352 was administered orally once‐daily (QD) at dose levels of 2, 4, 6, and 8 mg. The primary endpoints were dose‐limiting toxicity (DLT) and the maximum tolerated dose (MTD). This study is registered at ClinicalTrials.gov (NCT04631835).ResultsBetween August 2020 and March 2022, a total of 18 female patients were enrolled. DLT, manifested as hyperglycemia, occurred in two patients in the 8 mg QD group, establishing an MTD of 6 mg QD. The most common treatment‐related adverse events were hyperglycemia (88.9%) and weight loss (61.3%). In the 6 mg QD group, four patients (66.7%) had a partial response (PR), and one (16.7%) had stable disease (SD). Among the four patients with PIK3CA mutated tumors in this dosage group, three (75.0%) had PR and one (25.0%) had SD. The median progression‐free survival was not reached (95% confidence interval, 11.1‐NA).Discussion and ConclusionHS‐10352 at 6 mg QD was well‐tolerated in patients with HR‐positive, HER2‐negative ABC, and showed preliminary antitumor activity in patients with PIK3CA mutated tumors. These findings support the further clinical development of HS‐10352.
Subject
Cancer Research,Radiology, Nuclear Medicine and imaging,Oncology