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Neratinib

Tyrosine Kinase Inhibitors

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Tyrosine

240mg oral daily. Dosing will follow standard dose escalation procedures

Neratinib Oral Tablet

20mg oral twice daily. Dosing will follow standard initial dose recommendation procedure

Ruxolitinib Oral Tablet

Page E Blas, MA

Joyce A O'Shaughnessy, MD

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.

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.

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

Signaling signatures of research biopsies will be analyzed via Next Generation Sequencing and Reverse Phase Protein Array

Calculate objective response rate (CR+PR) associated with neratinib in combination ruxolitinib. Objective response rate will be calculated by defining the proportion of patients who have a complete or partial response to the study therapy, as determined by the treating physician.

Calculate duration of response associated with neratinib in combination with ruxolitinib. Duration of response will be calculated from the time of tumor response to disease progression in patients responding to study therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neratinib in Combination With Ruxolitinib in Patients With mTNBC	NCT06008275	Metastatic Trip... Breast Cancer	Neratinib Oral ... Ruxolitinib Ora...	18 Years -	Baylor Research Institute
Neratinib in Combination With Ruxolitinib in Patients With mTNBC	NCT06008275	Metastatic Trip... Breast Cancer	Neratinib Oral ... Ruxolitinib Ora...	18 Years -	Baylor Research Institute
Neratinib in Combination With Ruxolitinib in Patients With mTNBC	NCT06008275	Metastatic Trip... Breast Cancer	Neratinib Oral ... Ruxolitinib Ora...	18 Years -	Baylor Research Institute

Spots Global Cancer Trial Database for neratinib oral tablet