Leronlimab Combo Shows Promise for Metastatic TNBC in Early Phase 1b/2 Trial Data

Leronlimab Combo Shows Promise for Metastatic TNBC in Early Phase 1b/2 Trial Data

Investigational therapy leronlimab is showing promise as a potential therapy for people with CCR5-positive metastatic triple-negative breast cancer (mTNBC), early data from a Phase 1b/2 clinical trial suggest.

The open-label trial (NCT03838367) is testing a combination of leronlimab, also known as PRO 140 and developed by CytoDyn, plus chemotherapy agent carboplatin, in triple-negative breast cancer patients whose cancer is positive for the CCR5 protein and has spread to distant regions.

After eight weeks of treatment, the first patient in the trial showed no signs of circulating tumor cells or cells more prone to forming metastasis in the blood. The patient also had lower levels of CCR5, which has a tumor-promoting function, in cancer-associated cells.

This patient received eight weekly subcutaneous (under-the-skin) injections of leronlimab, at a dose of 700 milligrams, plus carboplatin. This is the highest leronlimab dose being tested in the trial.

“The fourth blood sample from the mTNBC patient, drawn following eight weeks of treatment, demonstrates a notably sustained response to leronlimab,” Bruce Patterson, MD, CEO of diagnostic company IncellDx, said in a press release.

“Other cancer-associated macrophage-like (CAML) cells in the blood sample were found at the lower limits of detection and were also decreased in size. Most importantly, the CAML cells had reduced CCR5 staining compared to samples taken from the patient three weeks earlier, reflecting an ongoing blockade of the CCR5 receptor by leronlimab,” Patterson added.

The trial is being conducted in two parts: Phase 1b to determine the optimal dose of leronlimab, and Phase 2 to measure how long patients live without the disease worsening after receiving the established dose. Phase 2 will also assess the proportion of patients responding to treatment, time to metastasis, change in circulating tumor cells, and overall survival, among other outcomes.

Researchers aim to enroll 48 participants in the trial, which is underway at the Quest Clinical Research in San Francisco, Northwestern University Feinberg School of Medicine, Houston Methodist, Vanderbilt University, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital. More information, including contacts and locations, can be found here.

Eligible patients must have received conventional chemotherapy with anthracyclines and taxanes during their initial therapy for localized disease, but have not received prior chemotherapy in the metastatic setting.

A second patient has been enrolled under an emergency investigational new drug (IND) application granted by the FDA in September 2019.

Pending similar results in this patient, CytoDyn plans to ask regulatory authorities to grant leronlimab breakthrough therapy designation by the end of the month to expedite the treatment’s development and review. It has already been granted fast track status by the U.S. Food and Drug Administration for metastatic triple-negative breast cancer.

Leronlimab is a human antibody designed to block the CCR5 surface receptor protein, whose levels are increased in several cancers, including triple-negative breast cancer. Preclinical studies have shown that by blocking CCR5, leronlimab stopped breast cancer cells from migrating — reducing metastasis by more than 98% in a mouse model — and made them more sensitive to chemotherapeutic agents.

Under an exclusive licensing agreement, IncellDx has the rights to use leronlimab for the development of assays that measure levels of CCR5 in human cells, which may potentially identify patients more likely to benefit from treatment.

“It is very exciting to see additional preliminary results that demonstrate leronlimab’s potential as a therapeutic option to treat mTNBC. We are also pleased to have enrolled a second patient with metastatic breast cancer under an emergency IND,” said Nader Pourhassan, PhD, president and CEO of CytoDyn.

“We have had many patients contact us for treatment under our expanded access protocol and another hospital has opened enrollment for our mTNBC trial. We look forward [to] continuing our research in furtherance of this clinical development plan,” Pourhassan added.