NCT02802098

Abrogation of Chronic Monoclonal Antibody Treatment-induced T-cell Exhaustion With DURVALUMAB in Advanced HER-2 Negative Breast Cancer

Abrogation of Chronic Monoclonal Antibody Treatment-induced T-cell Exhaustion With DURVALUMAB (MEDI4736) in Advanced HER-2 Negative Breast Cancer: a Pilot Proof-of-concept Trial

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Centro Nacional de Investigaciones Oncologicas CARLOS III · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single-arm pilot proof of concept, open-label clinical trial. Twenty-five subjects will be enrolled in 6 sites. Metastatic breast cancer patients with disease progression to bevacizumab maintenance treatment will be potential candidates. Bevacizumab maintenance will be considered as six weeks of bevacizumab treatment in monotherapy, with hormonal treatment or combined with chemotherapy in the context of previous bevacizumab plus chemotherapy regimens. When progression to bevacizumab maintenance treatment occurs, patients will enter the trial and will start receiving DURVALUMAB 10 mg/kg Q2W IV infusion plus bevacizumab 10mg/kg IV infusion every 2 weeks. The patients will undergo a tumor biopsy before the first dose of DURVALUMAB, and after one month of combined treatment - the blood sampling will continue on a monthly basis. The treatment will continue until disease progression.

Detailed description

Acquired resistance against chronic administration of the monoclonal antibody antiangiogenic agent like bevacizumab in breast cancer is caused in a fraction of patients by an immune reprogramming. The immune reprogramming can be detected by elevated counts of Tregs in peripheral blood, aberrant pattern of cytokines, and elevated concentrations of kynurenine and immunosuppressive/vasodilator prostaglandins. The addition of DURVALUMAB to a bevacizumab-based treatment would delay or abrogate these changes and be of therapeutic interest in this scenario.

Conditions

• Metastatic Breast Cancer
• Bevacizumab-alone Maintenance Treatment Progression

Interventions

Type	Name	Description
DRUG	Durvalumab	Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1). PD-L1 can be expressed by tumours to evade detection by the immune system through binding to PD-1 on cytotoxic T lymphocytes. Durvalumab blocks the PD-L1 interaction with PD-1, countering the tumour's immune-evading tactics.
DRUG	Bevacizumab	Bevacizumab is a recombinant humanized monoclonal antibody that blocks angiogenesis by inhibiting vascular endothelial growth factor A (VEGF-A)

Timeline

• Start date: 2016-05-01
• Primary completion: 2019-06-01
• Completion: 2019-07-01
• First posted: 2016-06-16
• Last updated: 2020-06-19

Locations

6 sites across 1 country: Spain