Entinostat Plus Pyrotinib and Endocrine Therapy in Advanced Triple-Positive Breast Cancer After Trastuzumab Failure
Summary
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.
Timeline
- Start
- 2025-06-23
- Primary completion
- 2027-02
- Completion
- 2027-02
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Entinostat | Small molecule | 3 mg | Oral |
| Subject | Entinostat | Small molecule | 4 mg | Oral |
| Subject | Entinostat | Small molecule | 5 mg | Oral |
| Subject | Pyrotinib | Small molecule | 400 mg | Oral |
| Background | Anastrozole | Other / unclassified | 1 mg | — |
| Background | Exemestane | Small molecule | 25 mg | — |
| Background | Fulvestrant | Small molecule | 500 mg | Intramuscular |
| Background | Letrozole | Other / unclassified | 2.5 mg | — |
| Background | Tamoxifen | Small molecule | 20 mg | — |