Bortezomib Followed by Pembrolizumab and Cisplatin in metTNBC

Breast Cancer Clinical Trial

Official title: Pilot Clinical Trial of Treatment With Bortezomib to Inhibit Homologous Recombination (HR) Followed by Pembrolizumab and Cisplatin in Patients With Chemotherapy-Pretreated Metastatic Triple Negative Breast Cancer

Status Recruiting

Clinical Trial Summary

The hypothesis of this pilot trial is that administration of bortezomib will inhibit NHEJ in metastatic TNBC leading at the time of disease progression to metastases that are HR-deficient and sensitive to pembrolizumab and cisplatin therapy. The trial will include in depth analysis of the patients' TNBC genome and phosphoproteome to evaluate HR-proficiency and deficiency, and nuclear proteins that drive NHEJ, before and upon progression with bortezomib therapy.

Clinical Trial Description

Seventy to 80% of breast cancers have a basal gene expression profile which is characterized by homologous recombination deficiency (HRD) and high proliferation. HRD leads to upregulation of the activity of the non-homologous end joining (NHEJ) error-prone pathway that repairs DNA double strand breaks, a process required for TNBC survival. The hypothesis of this pilot trial is that administration of bortezomib will inhibit NHEJ in metastatic TNBC leading at the time of disease progression to metastases that are HR-deficient and sensitive to pembrolizumab and cisplatin therapy. A patient with an exceptional complete and durable response of her primary-refractory metastatic TNBC with PI3K pathway inhibition followed at disease progression by nab paclitaxel/cisplatin provides the clinical rationale for the present trial which will utilize bortezomib to inhibit HR proficiency prior to administration of pembrolizumab and cisplatin in pretreated metastatic TNBC patients.

Patients will receive bortezomib until PD, followed by pembrolizumab and cisplatin until PD or a maximum of 6 cycles on study. If patients are responding, they may continue pembrolizumab at the physician's discretion off study. Metastatic TNBC patients will undergo core needle biopsies of a metastatic lesion at study entry and at disease progression from bortezomib for NGS, RPPA, and other molecular analyses.

Patients whose disease does not respond to pembrolizumab and cisplatin may be treated with standard of care breast cancer therapies off study, at the recommendation of the treating physician. ;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT04265872
• Study type: Interventional
• Source: Baylor Research Institute
• Contact: Page Blas, MA
• Phone: 214-820-5424
• Email: page.blas@bswhealth.org
• Status: Recruiting
• Phase: Early Phase 1
• Start date: October 15, 2020
• Completion date: December 1, 2024