NCT03012230

Pembrolizumab and Ruxolitinib Phosphate in Treating Patients With Metastatic Stage IV Triple Negative Breast Cancer

A Phase 1 Study of PD-1 Inhibition With Pembrolizumab Combined With JAK2 Inhibition in Triple Negative Breast Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of ruxolitinib phosphate when given together with pembrolizumab in treating patients with stage IV triple negative breast cancer that has spread to other places in the body. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ruxolitinib phosphate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and ruxolitinib phosphate together may work better in treating patients with stage IV triple negative breast cancer.

Detailed description

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) of ruxolitinib phosphate (ruxolitinib) (JAK2 inhibition) in combination with fixed dosing of pembrolizumab (anti PD-1) in patients with advanced/metastatic triple negative breast cancer (TNBC). SECONDARY OBJECTIVES: I. To determine the safety profile of pembrolizumab in combination with ruxolitinib. II. To estimate clinical tumor response in women with TNBC treated with pembrolizumab in combination with ruxolitinib as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. EXPLORATORY/CORRELATIVE OBJECTIVES: I. To assess tumor response with immune related (ir)RECIST and associations with PDJ amplification, PD-L1, PD-L2, JAK2 and phosphorylated (p)STAT3 expression. II. To determine the effect of combination targeted blockade on T- and B- cell immunity to breast cancer tumor antigens. OUTLINE: This is a dose-escalation study of ruxolitinib phosphate. Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed up every 3 or 6 months for up to 2 years.

Conditions

• Metastatic Malignant Neoplasm in the Bone
• Stage IV Breast Cancer AJCC v6 and v7
• Triple-Negative Breast Carcinoma

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
BIOLOGICAL	Pembrolizumab	Given IV
DRUG	Ruxolitinib Phosphate	Given PO

Timeline

• Start date: 2017-12-06
• Primary completion: 2023-01-06
• Completion: 2023-03-08
• First posted: 2017-01-06
• Last updated: 2024-01-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study