Outcomes
tumor, DLTs, SD, Cancer
ADVERSE EVENT, TUMOR, DISEASE, TUMOR PROGRESSION, CANCER
The primary study objectives were to assess the incidence of DLTs and establish the recommended dose and the maximum tolerated dose (MTD) of amcenestrant monotherapy in Japanese postmenopausal women with ER + /HER2 − advanced breast cancer. Secondary objectives were to characterize the overall safety profile, PK, and antitumor activity of amcenestrant monotherapy. AEs were graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.03) and classified according to the Medical Dictionary for Regulatory Activities (MedDRA version 23.1). The safety population included all patients who received at least one dose of amcenestrant.Plasma PK parameters were assessed in the safety population, at both doses, after single (C1D1) or repeated oral administration (C1D22) and reported as descriptive statistics. Additionally, plasma 4β-‍hydroxycholesterol (4β-OH cholesterol) and total cholesterol levels were quantified to assess the potential of amcenestrant to inhibit or induce CYP3A drug metabolizing enzymes.Antitumoral responses, including confirmed complete response (CR), partial response (PR), and stable disease (SD), or progressive disease were determined by the investigator according to RECIST v1.1. The objective response rate (ORR: CR + PR), clinical benefit rate (CBR: CR + PR + SD ≥ 24 weeks), and non-progression rate at 24 weeks were calculated for each dose level, including 90% confidence intervals (CI). Response duration (time from initial response to the first documented tumor progression) was calculated for each patient. The ‘response-evaluable’ population included patients who had measurable lesions at baseline and ≥ 1 evaluable tumor assessment.