Probably much better (complete, updated) ones ou

Probably much better (complete, updated) ones out there- but this is a write up from a while back I compiled to give to an oncologist friend. It is dated- as the trials were going on then.

If you would like it in the prettier Word version with active links- PM me for my email address and will be glad to send.

Best of luck to your friend, CGC

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Leronlimab Cancer Clinical Trial: Next Generation Monoclonal Antibody Therapy

Leronlimab (PRO 140) is a monoclonal antibody CCR5 receptor antagonist, to be used as a platform drug for a variety of indications.

How it Works: Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5, a cellular receptor that is important in HIV infection, tumor metastases, and other diseases, including NASH. The FDA has granted a Fast Track designation to CytoDyn for two potential indications of leronlimab for critical illnesses. Leronlimab has completed nine clinical trials in over 800 people and met its primary endpoints in a pivotal Phase 3 trial (leronlimab in combination with standard antiretroviral therapies in HIV-infected treatment-experienced patients).

In the setting of cancer, research has shown that CCR5 may play a role in tumor invasion, metastases, and tumor microenvironment control. Increased CCR5 expression is an indicator of disease status in several cancers. Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 98% in a murine xenograft model. CytoDyn is, therefore, conducting several human clinical trials to establish proof of concept and efficacy in patients with cancer. This includes a Phase 2 compassionate use study in metastatic triple-negative breast cancer (being granted Fast Track designation in May 2019) and a Phase 2 basket study on patients with CCR5 locally advanced or metastatic sold tumor.

o Taken Along with Current Treatment: The study treatment, Leronlimab (PRO 140), is a once per week subcutaneous injection. It can be used along with one’s current cancer treatment.

o Major possible benefits:
o Reducing metastasis: as CCR5/CCL5 is the axis that white blood cells use for chemotaxis
o Restoring Tumor microenvironment: as blocking CCR5 can repolarize White Blood Cells.
o In CCR5 over-expressing cancers: CCR5 over-expression seems to play a role in chemo and therapeutic resistance.. blocking CCR5 seems to increase effectiveness of therapies.

o Impeccable Safety Profile: Lack of SAEs, well tolerated, in more than one thousand patients over five years, in a population as fragile as HIV patients.

o Rapid Results:
o Trials are indicating drops CTC and reduction of EMT cells and putative metastic cells.
o Leronlimab may absolutely help even in advanced TNBC. Blocking CCR5 is being found to possibly reduce metastasis and reduce the ability of tumor cells to maintain the micro-environment that enables them to avoid other chemotherapies and the body's immune system.

Main Resources:
o Presentation at Triple Negative Breast Cancer Drug Development Digital Summit 2021 on April 28: https://d1io3yog0oux5.cloudfront.net/cytodyn/...o/TNBC.mp4
o Recent Advances Targeting CCR5 for Cancer and Its Role in Immuno-Oncology- in Cancer Research/ American Association of Cancer Research: Article available at: https://cancerres.aacrjournals.org/content/79/19/4801.long and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6810651/.
o Leronlimab’s Interaction with Cancer- Video (3 minutes):
o https://www.dropbox.com/s/3kpf69r21u7vasf/ler...2.mp4?dl=0
o The Role of the CCL5/CCR5 Axis in Cancer Progression
o https://res.mdpi.com/d_attachment/cancers/can...-01765.pdf
o Leronlimab, a humanized monoclonal antibody to CCR5, blocks breast cancer cellular metastasis and enhances cell death induced by DNA damaging chemotherapy https://rdcu.be/cd7b4
o www.cytodyn.com

o Clinical Trials including:
o Basket Study of Leronlimab (PRO 140) in Patients With CCR5+ Locally Advanced or Metastatic Solid Tumors
o A Compassionate Use Study of Leronlimab in Breast Cancer
https://clinicaltrials.gov/ct2/results?cond=&...&dist=

 
Clinical Trial Contacts
Clinical Research Coordinator
Jay Lalezari, MD <drjay@questclinical.com>


Additional Resources

Global Health Leaders Join CytoDyn's Scientific Advisory Board
Leading experts in the fields of HIV, Oncology, Rheumatology, and NASH join together to facilitate the best approaches to utilize multiple opportunities for leronlimab.
https://www.cytodyn.com/investors/news-events...c-advisory

Mechanism of Action Animation for leronlimab in Immuno-Oncology
Potential of leronlimab to positively influence the tumor microenvironment by inhibiting T-reg infiltration, conversion of M2 macrophages (protumor macrophages) into M1 macrophages (antitumor macrophages), decreasing tumor angiogenesis, and inhibiting metastasis through CCR5 overexpression.
https://www.youtube.com/watch?v=uxkc6Ql1C-U


Leronlimab Moving Toward Breakthrough Designation with Positive mTNBC Data
(Targeted Oncology)
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.
https://www.targetedonc.com/view/leronlimab-m...mtnbc-data
Leronlimab Provides a Significant Survival Benefit in Metastatic Triple-Negative Breast Cancer (https://www.cancernetwork.com/view/leronlimab-provides-a-significant-survival-benefit-in-metastatic-triple-negative-breast-cancer)
A review of antibody-based therapeutics targeting G protein-coupled receptors: an update
Expert Opinion on Biological Therapy: Journal (Volume 20, 2020 - Issue
There are currently two approved GPCR-targeting mAbs; these are mogamulizumab and erenumab which target CCR4 and CGRP type 1 receptor, respectively. One other mAb is at an advanced stage of clinical development, namely leronlimab (or PRO140) that targets CCR5. Summary case studies are presented. https://www.tandfonline.com/doi/full/10.1080/...20.1745770

CCR5's Role in Cancer Metastasis, Leronlimab and Cancer
https://www.cytodyn.com/pipeline/cancer

Useful Links on this website (with links):
CCR5 Antagonist Blocks Metastasis of Basal Breast Cancer Cells
Link: Read Article
CCR5 Receptor Antagonists Block Metastasis to Bone of v-Src Oncogene-Transformed Metastatic Prostate Cancer Cell Lines
Link: Read Article
The CCL5/CCR5 Axis Promotes Metastasis in Basal Breast Cancer
Link: Read Article
CCR5 Governs DNA Damage Repair and Breast Cancer Stem Cell Expansion
Link: Read Article
Tumoral Immune Cell Exploitation in Colorectal Cancer Metastases Can Be Targeted Effectively by Anti-CCR5 Therapy in Cancer Patients
Link: Read Article
CytoDyn aims to be ‘paradigm-shifting’ in cancer management with its platform drug Leronlimab (PRO 140)
Link: Watch Video