BGB-43395 + letrozole

BGB-43395 + letrozole is a combination therapy being investigated in clinical trials for hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer and other advanced solid tumors. This combination pairs BGB-43395, a selective cyclin-dependent kinase 4 (CDK4) inhibitor, with letrozole, an established aromatase inhibitor used in hormone therapy. The combination is currently being studied in Phase 1 clinical trials, with the main purpose of determining the recommended dosing, safety profile, and preliminary efficacy. According to the search results, BGB-43395 is administered orally twice daily (morning and evening), while letrozole is taken orally once daily. The combination is being evaluated in a multi-part clinical trial (NCT06120283) that includes: - Part A: BGB-43395 as monotherapy - Part B: BGB-43395 in combination with fulvestrant - Part C: BGB-43395 in combination with letrozole This study is actively recruiting participants at multiple sites globally, including centers in the United States, Thailand, and China. A separate trial (NCT06253195) is also evaluating this combination specifically in Chinese participants with HR+/HER2- breast cancer and other advanced solid tumors. The primary objectives of these trials are to assess safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose or maximum administered dose and the recommended dose for expansion. Secondary endpoints include evaluating preliminary antitumor activity according to RECIST v1.1 criteria. Eligible participants for the trials typically include: - Patients with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors associated with CDK4 dependency - Patients with HR+/HER2- breast cancer who have received prior therapy including endocrine therapy and a CDK4/6 inhibitor - Female participants with metastatic HR+/HER2- breast cancer must be postmenopausal or receiving ovarian function suppression - Male participants with HR+/HER2- breast cancer require gonadal suppression using GnRH agonists when being treated with letrozole. The combination therapy represents an investigational approach for patients who have progressed on prior treatments, potentially offering a new option for those with limited therapeutic alternatives.