Leronlimab Moving Toward Breakthrough Designation With Positive mTNBC Data

The FDA has recommended that a preliminary meeting for a potential Breakthrough Therapy designation be requested for leronlimab as a treatment of patients with metastatic triple-negative breast cancer, based on positive data from a phase Ib/II study.

The FDA has recommended that a preliminary meeting for a potential Breakthrough Therapy designation be requested for leronlimab (PRO 140) as a treatment of patients with metastatic triple-negative breast cancer (TNBC), based on positive data from a phase Ib/II study, CytoDyn, developer of the CCR5 antagonist, announced in a press release.

The first patient was enrolled in the study and received their first treatment in September of 2019. Following 2 treatments with leronlimab and carboplatin, the patients’ circulating tumor cells (CTC) decreased to 0. Additionally, the total CTC and epithelial mesenchymal transition in tumor metastasis (EMT) levels decreased to 0 after a month of weekly treatments.

A CT scan was given to the patient to measure tumor shrinkage and showed a 25% reduction in size within a few weeks of treatment with leronlimab and carboplatin. The patient had 0 detectible cancer-associated microphage-like cells, in addition to continuing to show no CTCs or EMTs after about 5 months of treatment. Since these results were recorded, the patient has discontinued treatment with carboplatin but continues treatment with leronlimab at the oncologist’s recommendation.

“Our first patient in the phase Ib/II trial has shown remission of the tumor and her oncologist has attributed this primarily to leronlimab and discontinued the carboplatin (a form of chemotherapy). This patient’s latest results of zero CTC, EMT, and CAML are unique and we now have another patient with 3 zeros identical to the first patient. We are very excited to continue enrolling patients and hopeful to have our first patient treated in our basket trial for 22 solid tumor cancers very soon,” said Nader Pourhassan, PhD, president and CEO of CtyoDyn, in a statement. “We are also very hopeful to have several more patients in our phase Ib/II mTNBC trial before our preliminary meeting with the FDA for Breakthrough Therapy designation.”

The ongoing study consists of 4 experimental arms, 3 of which were included in the phase I stage, and 1 in the phase II stage. Patients in phase I receive either leronlimab 350 mg, 525 mg, or 700 mg of leronlimab weekly plus carboplatin AUC 5 every 3 weeks. In phase II, patients receive the maximum tolerated dose (MTD) of leronlimab plus carboplatin AUC 5.

The primary end point of phase Ib was to determine the MTD of leronlimab when combined with carboplatin. The primary end point of phase II is progression-free survival (PFS). The secondary end points of phase II include PFS per RECIST v1.1 criteria in patients with PD-L1 expression; overall response rate; time to new metastases; the change in CTC level in the peripheral blood from baseline; overall survival, and the number, frequency, and severity of adverse events to evaluate the safety of leronlimab.

The study included patients with histologically confirmed TNBC who were positive for CCR5 by immunohistochemistry. Eligible patients were also a minimum of 18 years old with an ECOG performance status of 0 to 1, a life expectancy of at least 6 months, and adequate organ and bone marrow function.

Patients who presented with HER2 overexpression orHER2-amplified metastatic breast cancer (MBC), ER and PR expressing tumors, prior systemic chemotherapy for MBC, active infection, active central nervous system metastasis, and other conditions that had the potential to interfere with the results, were excluded from the study.

Preclinical research has shown that CCR5 is important for tumor invasion and metastasis, and increased expression of CCR5 is indicative of disease status in several cancers. Studies in animal models have also shown that blocking CCR5 can reduce tumor metastases in prostate cancer.

Leronlimab also received an Orphan Drug designation from the FDA for the prevention of graft-versus-host disease (GVHD), based on preclinical studies. A phase II study was initiated to explore its activity in the treatment of GVHD further. The agent is also being explored as a potential treatment for HIV and other diseases.


CytoDyn’s first MTNBC patient in phase 1b/2 is in remission and oncologist ordered termination of treatment with carboplatin (chemotherapy drug) and remains on leronlimab only as monotherapy; patient’s testimony about her condition after nearly 6 months of leronlimab treatment is very strong [news release]. Vancouver, Washington: CytoDyn, Inc; March 12, 2020.https://bit.ly/2xxXxHE. Accessed March 12, 2020.

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