FDA Grants Fast Track Designation to Leronlimab for Metastatic TNBC

Richard Pestell, MD, PhD

The FDA has granted a fast track designation to the CCR5 antagonist leronlimab (PRO140) for use in combination with carboplatin for the treatment of patients with CCR5-positive metastatic triple-negative breast cancer (TNBC).

The agent, which is administered via injection, is being evaluated in clinical trial at sites that are initiating patient enrollment, such as Quest Clinical Research in San Francisco, Northwestern University Medical School, Methodist Houston, Vanderbilt University, and Sidney Kimmel Cancer Center, CytoDyn, the developer of the antagonist, stated in a press release.

“This is an important acknowledgement of the potentially paradigm-shifting therapy option in metastatic triple-negative breast cancer,” Richard Pestell, MD, PhD, vice chairman and chief medical officer of CytoDyn, said in the press release. “Currently, there are no enduring treatment options for mTNBC patients, and we thank the FDA for recognizing the potential of leronlimab for mTNBC patients.”

The company also stated that injection of the first patient with metastatic TNBC is expected to be imminent.

Fast track designation is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

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. The agent has also been granted a fast track designation to leronlimab combined with highly active antiretroviral therapy for patients with HIV infections.

Prior research has shown that CCR5 potentially plays a central role in tumor invasion and metastasis and that increased CCR5 expression is an indicator of disease status in several cancers. Additional data demonstrated that CCR5-blocking drugs can block tumor metastases in laboratory and preclinical models of aggressive breast and prostate cancer.

The company is conducting additional research with leronlimab in select malignancies, with plans to initiate phase II trials beyond the one in TNBC.

“We remain highly encouraged by the potential of leronlimab (PRO 140) as a pipeline of opportunities within a single drug franchise,” Nader Pourhassan, PhD, president, CEO and director of CytoDyn, said in the press release.

Moreover, the CCR5 receptor also potentially has a central role in modulating immune cell trafficking to inflammation sites, and it may be crucial for the development of acute GVHD and other inflammatory conditions. CytoDyn also stated that blocking CCR5 with a chemical inhibitor can reduce the clinical impact of acute GVHD without affecting the engraftment of transplanted bone marrow stem cells.

A phase II trial with leronlimab is being conducted to determine whether CCR5 receptor on engrafted cells is necessary for the development of acute GVHD and, by blocking it, researchers could recognize that select immune signaling molecules is a viable approach to mitigating acute GVHD. The FDA also granted an orphan drug designation to leronlimab as a prevention method of GVHD.

FDA Grants CytoDyn Fast Track Designation for Leronlimab (PRO 140) in metastatic Triple-Negative Breast Cancer, an Unmet Medical Need. CytoDon. Published May 7, 2019. https://bit.ly/2DWHsLT. Accessed May 7, 2019.