Entinostat Plus Pyrotinib and Endocrine Therapy in Advanced Triple-Positive Breast Cancer After Trastuzumab Failure

Sponsor
Tianjin Medical University Cancer Institute and Hospital
Study ID
NCT07708194
Phase
PHASE1/PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • entinostat — DRUG
    Entinostat is an oral, selective class I histone deacetylase (HDAC) inhibitor, administered at 3 mg, 4 mg, or 5 mg once weekly on Days 1, 8, 15, and 22 of each 28-day cycle, taken 60 minutes after a meal. The dose is determined by the 3+3 dose-escalation design in Part Ib.
  • Pyrotinib — DRUG
    Pyrotinib is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor, administered at a fixed dose of 400 mg once daily, taken 30 minutes after a meal, in each 28-day cycle.
  • endocrine therapy — DRUG
    Physician-selected endocrine therapy based on patient's prior treatment history and menopausal status. Options include tamoxifen (20 mg daily), aromatase inhibitors (letrozole 2.5 mg daily, anastrozole 1 mg daily, or exemestane 25 mg daily), or fulvestrant (500 mg intramuscularly on Days 1, 15, 29, and once monthly thereafter). For premenopausal patients, ovarian function suppression (OFS) with GnRH agonists is added. All endocrine agents are administered according to their approved package inserts.

Study Details

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.

Key Dates

First listed
Jul 16, 2026
Start date
Jun 23, 2025
Status verified
Jul 2026
Primary completion
Feb 28, 2027
Completion
Feb 28, 2027

Study Design

Enrollment
94 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Entinostat + Pyrotinib + Endocrine Therapy
    Participants receive entinostat (weekly, oral), pyrotinib (400 mg daily, oral), and physician-selected endocrine therapy (tamoxifen, aromatase inhibitor, or fulvestrant; plus OFS for premenopausal patients) in 28-day cycles. Part Ib: dose-escalation of entinostat (3 mg, 4 mg, 5 mg) following the 3+3 design to determine MTD/RP2D. Part II: expansion at RP2D to evaluate efficacy and safety.

Primary Outcome Measure

Dose-Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD), and Recommended Phase II Dose (RP2D) of Entinostat in Combination with Pyrotinib and Endocrine Therapy [ Time Frame: Cycle 1 (Day 1 to Day 28) ]

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