Leronlimab Continues to Demonstrate Early Promise in CCR5+ Metastatic TNBC

Nader Pourhassan, PhD

Leronlimab (PRO140) was found to improve survival in patients with CCR5-positive metastatic triple-negative breast cancer (TNBC) in whom at least 2 prior lines of therapy had failed, according to data from an updated analysis of a Compassionate Use Study, a phase 1b/2 study, and from a basket study.¹

Seventy-five of patients who had a lower level of circulating cells either following treatment with lenrolimab (86%) or at baseline (14%) demonstrated a 3600% increase in overall survival (OS) at 12 months (P = .0004) vs a 980% increase in OS that had previously been reported by CytoDyn Inc., the drug developer, on August 25, 2021.

“We believe these updated results are very strong,” Nader Pourhassan, PhD, president and chief executive officer of CytoDyn, Inc., stated in a press release. “Our chief operating officer, Dr Nitya Ray, is leading our team in preparing a breakthrough therapy application to be submitted to the FDA this week.”

Lenrolimab is an investigational humanized IgG4 monoclonal antibody that binds to CCR5, which is a critical cellular receptor that plays an important role in human immunodeficiency virus, tumor metastases, and other diseases like nonalcoholic steatohepatitis.

Previously, data from a 12-month analysis of phase 1b/2 trial (NCT03838367) indicated that lenrolimab was combined with carboplatin it reduced cancer-associated macrophage-like cells (CAMLs) by 72%, and this was associated with about a 450% increase in overall survival in 30 patients with metastatic TNBC.² These decreases in CAMLs were observed following just 4 doses of the agent and at approximately 30 days after induction. The reduction in CAMLs was also linked with an approximate 300% increase in mean progression-free survival (PFS) in this population.

High CCR5 was noted in tumor tissue biopsies, and investigators indicated that this could be used to stratify patients who were likely to experience progressive disease with leronlimab. Moreover, it was suggested that decreases in CAMLs and circulating tumor cells could be associated with slower disease progression and reduced mortality. CAMLs could also help identify those who will achieve responses with the agent.

The FDA granted a fast track designation to leronlimab for use in combination with carboplatin in patients with CCR5-positive metastatic TNBC in May 2019,³ and the agent has also received fast track status for use in combination with antiretroviral therapy in patients infected with HIV.

Previous research efforts have indicated that CCR5 has a central role in tumor invasion and metastasis, and that increased expression could be indicative of disease status in a variety of malignancies. Additional findings from laboratory and preclinical models of aggressive breast and prostate cancers have suggested that drugs that block CCR5 could block tumor metastases.

The CCR5 receptor may also have a key role in modulating immune cell trafficking to inflammation sites and could be crucial for the development of acute graft-versus-host disease (GVHD) and other inflammatory conditions. Blocking CCR5 with a chemical inhibitor could reduce the clinical impact of acute GVHD without impacting the engraftment of transplanted bone marrow stem cells.

In a murine xenograft model, leronlimab was found to reduce human breast cancer metastasis by more than 97%. Based on these early findings, the company has launched 2 ongoing clinical trials: a phase 2 trial that is examining the drug in patients with metastatic TNBC, and a phase 2 basket trial (NCT04504942) that is being done in patients with 22 different solid tumor cancers.

References

1. CytoDyn announces cancer update: 12-month analysis of 28 mTNBC patients receiving leronlimab suggest an increase of 3600% in 12-month OS in 75% of patients with a lower level of circulating cells after leronlimab induction or at baseline; 12-month PFS continues at near 600% increase. News release. CytoDyn, Inc. November 3, 2021. Accessed November 4, 2021. https://bit.ly/3mKIFg1
2. CytoDyn announces preliminary results from 30 mTNBC patients treated with leronlimab. Decreases in CAMLs after 4 doses of leronlimab were indentified in over 70% of patients and were associated with a 450% significant increase in overall survival at 12-month analysis. News release. CytoDyn Inc. July 19, 2021. Accessed November 4, 2021. https://bit.ly/3kCOZ8X
3. FDA grants CytoDyn fast track designation for leronlimab (PRO 140) in metastatic triple-negative breast cancer, an unmet medical need. CytoDyn Inc. May 7, 2019. Accessed November 4, 2021. https://bit.ly/2DWHsLT