Lenrolimab Plus Chemo Demonstrates Substantial Survival Benefit in Metastatic TNBC

Scott Kelly, MD

Induction with lenrolimab (PRO140) resulted in an improvement in modified progression-free survival (mPFS) and modified overall survival (mOS) in patients with metastatic triple-negative breast cancer (mTNBC), according to data from a phase 1/2 trial (NCT04313075).¹

Of the 30 patients on the study, 73% experienced decreases in circulating tumors cells (CTCs) following lenrolimab induction. These decreases, which were reported using the LifeTracDx test, were linked with a 400% to 660% increase in mPFS/12-month PFS and a 570% to 980% increase in mOS/12-month OS.

The findings support the hypothesis that most patients respond to the CCR5 antagonist if CTC reduction is noted after 1 dose of the agent.

“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,” Scott Kelly, MD, chief medical officer and chairman of the board at CytoDyn Inc., stated in a press release. “…We believe this is further evidence that lenrolimab has a promising role in the future of oncology to help alleviate the burden of cancer on patients and their loved ones.”

An investigational humanized IgG4 monoclonal antibody, lenrolimab was designed to bind to the cellular receptor CCR5, which plays a key role in HIV infection, tumor metastases, and other disease such as nonalcoholic steatohepatitis.

Preliminary data from a 12-month analysis of the trial showed that the combination of lenrolimab and carboplatin resulted in a 72% reduction in cancer-associated macrophage-like cells (CAMLs), which was associated with an approximate 450% increase in OS.²

The decreases in CAMLs were observed after just 4 doses of the agent; this occurred approximately 30 days after induction with lenrolimab. The reduction in CAMLs was also noted to be linked with an approximate 300% increase in mean PFS in this patient population.

High CCR5 was noted in tumor tissue biopsies could help to stratify patients who are likely to experience progressive disease on the agent. Additionally, reductions in CAMLs and CTCs could be associated with slower progression and reduced mortality. Moreover, CAMLs could potentially identify patients who might respond to lenrolimab.

In the phase 2 basket trial (NCT04504942), leronlimab is under exploration in 30 patients with CCR5-positive locally advanced or metastatic solid tumors.³ To be eligible for enrollment, patients had to be receiving a standard anticancer treatment, be unable to receive standard therapy, or not have standard treatment available.

Patients also needed to have CCR5 positivity per immunohistochemistry, measurable disease per RECIST v1.1 criteria, be at least 18 years of age, have an ECOG performance status of 0 or 1, a life expectancy of at least 6 months, and adequate organ and bone marrow function within 28 days before registration, among other criteria.

In the trial, study participants will receive the agent via a subcutaneous administration at a weekly dose of 525 mg until progressive disease or unacceptable toxicity. Patients will be allowed to receive or to continue standard chemotherapy or radiotherapy in accordance with the dosing schedule included on the package insert.

The primary end points of the trial comprise the number, frequency, and severity of adverse effects, the incidence of abnormal laboratory test results, and changes in ECOG performance status from baseline to subsequently scheduled visits. Important secondary end points were PFS, ORR, clinical benefit rate, time to new metastases, changes from baseline in CTCs, and OS.

In May 2019, the FDA granted a fast track designation to lenrolimab for use in combination with carboplatin in the treatment of patients with CCR5-positive, metastatic TNBC.⁴ The drug also received a fast track designation for use in combination with antiretroviral therapy in patients with HIV infections.

References

1. CytoDyn’s final mTNBC report indicates as much as 980% increase in 12-month overall survival and up to 660% in 12-month modified progression free survival. News release.CytoDyn Inc. August 25, 2021. Accessed August 25, 2021. https://bit.ly/3sLVpEy
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 August 25, 2021. https://bit.ly/3kCOZ8X
3. Basket study of leronlimab (PRO 140) in patients with CCR5+ locally advanced or metastatic solid tumors. ClinicalTrials.gov. Updated August 7, 2020. Accessed August 25, 2021. https://clinicaltrials.gov/ct2/show/NCT04504942
4. 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 August 25, 2021. https://bit.ly/2DWHsLT