This is an open-label, single-center, exploratory, Phase Ib/II clinical trial evaluating the safety and efficacy of entinostat combined with pyrotinib and endocrine therapy in patients with advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer who have failed prior trastuzumab-based therapy.
The study consists of two parts: Part I (Phase Ib) employs a 3+3 dose-escalation design to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and recommended Phase II dose (RP2D) of entinostat when given in combination with pyrotinib (400 mg daily) and endocrine therapy. Part II (Phase II) uses a Simon two-stage design to further evaluate the efficacy and safety of the combination at the RP2D. The primary efficacy endpoint is progression-free survival (PFS) based on RECIST v1.1. A total of approximately 79-94 participants will be enrolled.
Age ≥ 18 and ≤ 75 years, female, premenopausal or postmenopausal.
Histologically confirmed HR+/HER2+ breast cancer (HER2 positive defined as IHC 3+ or FISH confirmed by the pathology department of the study center).
Histologically confirmed locally advanced breast cancer (not amenable to curative local therapy) or recurrent/metastatic breast cancer.
Prior treatment with trastuzumab and taxane-based anticancer therapy.
Factors significantly affecting oral drug absorption, such as inability to swallow, chronic diarrhea, or intestinal obstruction.
Prior treatment with any HDAC inhibitor for antitumor therapy.
Prior or current use of any HER2-targeted tyrosine kinase inhibitor (including lapatinib, neratinib, pyrotinib, etc.).
Known allergy to any component of the study drugs.
Tianjin Medical University Cancer Institute and Hospital
Lead sponsor
Taizhou EOC Pharma Co., Ltd.
Collaborator