Leronlimab Provides a Significant Survival Benefit in Metastatic Triple-Negative Breast Cancer

Leronlimab yielded a notable increase in overall survival and progression-free survival in patients with metastatic triple-negative breast cancer.

The use of leronlimab (PRO 140) in patients with metastatic triple-negative breast cancer (mTNBC) resulted in a notable increase in both overall survival (OS) and progression-free survival (PFS), according to a press release on a phase 1b/2 trial (NCT04313075) from CytoDyn.1

Investigators reported that patients who received leronlimab (n = 30) experienced a 400% to 660% increase in mean PFS (mPFS)/PFS and 12-month PFS, as well as a 570% to 980% increase in 12-month mOS/OS. Additionally, a 73% decrease in circulating tumor cells was observed in this patient population.

“We are delighted with the results of both mPFS and mOS when compared to the Standard of Care treatment for mTNBC across Emergency Use, Compassionate Use, mTNBC, and our Basket Trial. We anticipate the demand for new therapeutic options with limited toxicity and enhanced convenience for the patient to grow exponentially over the next decade,” Scott Kelly, MD, chief medical officer and chairman of the board at CytoDyn, said in a press release.

Leronlimab is a humanized IgG4 monoclonal antibody to the chemokine receptor CCR5.The non-randomized open-label study included 30 patients who were treated with leronlimab at a weekly dose of 350 mg until experiencing disease progression or intolerable toxicity. The placebo arm was treated with investigator’s choice of chemotherapy, including eribulin, gemcitabine, capecitabine, paclitaxel, nab-paclitaxel, vinorelbine, ixabepilone, or carboplatin.

Eligible patients were required to have histologically confirmed, locally recurrent or metastatic TNBC and be CCR5-positive by immunohistochemistry testing. Patients needed to either provide tissue from a new core or excisional biopsy or tumor lesion in order to enroll. Disease needed to be measurable by RECIST v1.1 criteria with an ECOG performance status of 0 or 1. Notably, those with HER2 overexpression or amplification, estrogen receptor– or progesterone receptor–expressing tumors, who are PD-L1–positive and eligible for atezolizumab (Tecentriq), or were part of another study featuring an investigational agent were not eligible to enroll on the trial

Additionally, preliminary findings from a phase 1b/2 clinical trial (NCT03838367) indicated that a combination of leronlimab and carboplatin yielded potentially promising outcomes in a population of patients with mTNBC.2 After 30 days of treatment, the CCR5 antagonist, which is designed to target multiple therapeutic markers, and carboplatin resulted in a 72% decrease in cancer-associated macrophage-like cells (CAMLs). The decrease in CAMLs was associated with a 300% decrease in mPFS and a 450%increase in mOS.

“This report of results for 30 patients suggests that, with one blood test, we may be able to predict which [patients with] mTNBC will respond well to leronlimab, which is a truly remarkable finding. These exploratory findings will now enable us to proceed for further regulatory review,” Nader Pourhassan, PhD, president and chief executive officer at CytoDyn, concluded.

Leronlimab has currently been granted fast track designation for 2 potential indications, including for Human Immunodeficiency Virus (HIV) and those with metastatic cancer.

Reference:

1. CytoDyn’s final mTNBC report indicated as much as 980% increase in 12-month overall survival and up to 660% in 12-month modified progression free survival. News Release. CytoDyn. August 25, 2021. Accessed August 25, 2021. https://bit.ly/3sN4ixV

2. CytoDyn announces preliminary results from 30 mTNBC patients treat with leronlimab. Decreases in CAMLs after 4 doses of leronlimab were identified in over 70% of patients and were associated with a 450% significant increase in overall survival at 12-month analysis. News Release. CytoDyn. July 19, 2021. Accessed August 25, 2021. https://bit.ly/3wUltxM