Leronlimab Granted Fast Track Designation in Metastatic Triple-Negative Breast Cancer
Posted: Wednesday, May 15, 2019
The U.S. Food and Drug Administration (FDA) recently granted Fast Track designation to leronlimab (PRO140) for use in combination with carboplatin for the treatment of patients with CCR5-positive metastatic triple-negative breast cancer. Clinical trial sites include Quest Clinical Research in San Francisco, along with four others that are in the process of initiating patient enrollment: Northwestern University Medical School, Methodist Houston, Vanderbilt University, and Sidney Kimmel Cancer Center. In addition, the FDA has granted Orphan Drug designation to leronlimab for the prevention of graft-versus-host disease.
Leronlimab is an investigational humanized IgG4 monoclonal antibody that blocks CCR5, a cellular receptor that appears to play multiple roles with implications in HIV infection, tumor metastases, and immune signaling. Leronlimab has successfully completed 9 phase I/II/III clinical trials in more than 700 people, including a phase III trial in combination with standard antiretroviral therapies in HIV-infected, treatment-experienced patients.
In the setting of cancer, research has shown that CCR5 likely plays a central role in tumor invasion and metastasis, and increased CCR5 expression appears to be an indicator of disease status in several cancers. Moreover, research has shown that drugs that block CCR5 can impede tumor metastases in laboratory and animal models of aggressive breast and prostate cancers.
The CCR5 receptor also seems to play a central role in modulating immune cell trafficking to sites of inflammation and may be important in the development of acute graft-versus-host disease and other inflammatory conditions. Clinical studies further support the concept that blocking CCR5 using a chemical inhibitor may reduce the clinical impact of acute graft-versus-host disease without significantly affecting the engraftment of transplanted bone marrow stem cells.