Phase Ib Clinical and Pharmacodynamic Study of the TIE2 Kinase Inhibitor Rebastinib with Paclitaxel or Eribulin in HER2-Negative Metastatic Breast Cancer.

ABSTRACT:

Purpose

Breast cancer cells disseminate to distant sites via tumor microenvironment of metastasis (TMEM) doorways. The TIE2 inhibitor rebastinib blocks TMEM doorway function in the PyMT mouse model of breast cancer. We aimed to assess the safety and pharmacodynamics of rebastinib plus paclitaxel or eribulin in patients with HER2-negative metastatic breast cancer (MBC).

Patients and methods

This phase Ib trial enrolled 27 patients with MBC who received 50 mg or 100 mg of rebastinib orally twice daily in combination with weekly paclitaxel 80 mg/m2 (if ≤2 prior non-taxane regimens) or eribulin 1.4 mg/m2 on days 1 and 8 (if ≥1 prior regimen). Safety, tolerability, and pharmacodynamic parameters indicating TIE2 kinase inhibition and TMEM doorway function were evaluated.

Result

SUBMITTER: Anampa JD 

PROVIDER: S-EPMC11818423 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature