NCT06008275

Neratinib in Combination With Ruxolitinib in Patients With mTNBC

Pilot Clinical Trial Examining the Safety and Efficacy of Neratinib in Combination With Ruxolitinib in Patients With Chemotherapy-pretreated Metastatic Triple Negative Breast Cancer With Chest Wall Recurrence

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Baylor Research Institute · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to assess the safety and efficacy of combined ruxolitinib and neratinib in patients with chemotherapy-pretreated metastatic triple negative breast cancer. This trial will evaluate one dosing schedule of neratinib in ruxolitinib in patients with metTNBC with locoregional recurrence.

Detailed description

Metastatic triple negative breast cancer (metTNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), making it unresponsive to both endocrine and HER2-targeted therapies. Chest wall recurrence is common in patients with treatment resistant metTNBC and leads to substantial morbidity as no successful therapeutic options exist. Patients suffer with escalated progression of disease across the entire chest wall with substantial wound control issues. Chest wall recurrence generally occurs within one year following chemotherapy or immunotherapy given with curative intent, and in general signifies metTNBC that is primary resistant to standard therapy. There is long standing evidence that EGFR is an important signaling pathway in metTNBC as this cancer overexpresses EGFR compared to other breast cancer subtypes. This exposes a pathway that is targetable for treatment, making EGFR a compelling molecular therapeutic target in metTNBC. Another key contributor to progression of TNBC is the JAK/STAT3 signaling pathway and assessments of EGFR have shown that it is a positive regulator of STAT3 that drives proliferation and survival of metTNBC. The investigators hypothesize that combined inhibition of EGFR and JAK/STAT3 using neratinib and ruxolitinib will lead to greater inhibition of the critically important EGFR pathway in TNBC with greater efficacy than targeting EGFR or JAK/STAT3 alone.

Conditions

• Metastatic Triple-Negative Breast Carcinoma
• Breast Cancer

Interventions

Type	Name	Description
DRUG	Neratinib Oral Tablet	240mg oral daily. Dosing will follow standard dose escalation procedures
DRUG	Ruxolitinib Oral Tablet	20mg oral twice daily. Dosing will follow standard initial dose recommendation procedure

Timeline

• Start date: 2024-09-16
• Primary completion: 2026-06-01
• Completion: 2026-12-01
• First posted: 2023-08-23
• Last updated: 2025-11-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study