Have said before that Oncology is the big prize for us. There is ample scientific body of research signaling to RANTES/CCR5 as a key player in this area:
Leronlimab's MOAs for cancer - Inhibits angiogenesis, shuts down cancer reappearing through collagen downregulation, Stops the recruitment of Tregs to tumor sites (Tregs promote tumor immunity), inhibits tumor cell dna repair, inhibits IL-13 a tumor protectant, downregulates IL-4 (IL-4 promotes tumor immunity), upregulates IFN-gamma promoting tumor cell death, downregulates PD-1/PD-L1, polarization of macrophages , downregulates calcium channel signaling, blocks CCL5 shutting down pathways for CTCs.
This is why we have a BASKET trial with 22 types of cancer. FDA does not give this as candy in Halloween.
There is a key element of monitoring/diagnosing and caring for cancer patients: CTC and CAM counts have been deemed to be a very good measure of the progression of the illness, some papers (of many more) related to this subject below:
CAML study related to my previous post from the Journal of Clinical Oncology.
https://ascopubs.org/doi/abs/10.1200/JCO.2017...uppl.11503
Role of Circulating Tumor Cell (CTC) Monitoring in Evaluating Prognosis of Triple-Negative Breast Cancer Patients in China
ttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493060/
The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper
https://www.sciencedirect.com/science/article...via%3Dihub
48 non-small cell lung cancer Patients Circulating Tumor Cell Assessment in Presumed Early Stage Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy: A Prospective Pilot Study
https://pubmed.ncbi.nlm.nih.gov/30244877/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912467/
For breast cancer, the article summarized the completed and ongoing clinical trials (as of 2019) using CTC number or phenotype for treatment decisions (7 studies).
https://www.medpagetoday.com/meetingcoverage/...lsmm/87147
Medpage article (June 2020) on Prostate cancer discussing a large phase III randomized clinical trial, SWOG S1216, a study run by the NCI Southwest Oncology Group.
As we all know, metastasis is responsible for a large percentage of mortality on Oncology.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597235/
The estimation is that 90% of deaths are from metastatic cancer. That is, if LL indeed can reduce CTCs and CAMLs we will have a substantial impact on clinical outcomes for patients (substantial might be an understatement).
The conclusion is clear: CTCs are a biomarker of overall survival rate (ORS). A CTC threshold of 5 cells per 7.5 ml defines to a great extent ORS in several types of cancers.
Most of oncology drugs objective is to extent ORS for patients. This defines the success (or lack off) of a therapy.
As a remainder from previous conferences:
So, we need as much information as we can get of the current status of the Cancer patients (from basket trial and otherwise). A reduction of counts means “we have a signal” as NP says. And a very strong one I might add. Reducing CTC 7 CAMS counts = OS extension (big time).
Are we still reducing CTCs ????. What is the status after several months (years) of treatment ???
Pleaaaaseeeee tell us …..
Leronlimab's MOAs for cancer - Inhibits angiogenesis, shuts down cancer reappearing through collagen downregulation, Stops the recruitment of Tregs to tumor sites (Tregs promote tumor immunity), inhibits tumor cell dna repair, inhibits IL-13 a tumor protectant, downregulates IL-4 (IL-4 promotes tumor immunity), upregulates IFN-gamma promoting tumor cell death, downregulates PD-1/PD-L1, polarization of macrophages , downregulates calcium channel signaling, blocks CCL5 shutting down pathways for CTCs.
This is why we have a BASKET trial with 22 types of cancer. FDA does not give this as candy in Halloween.
There is a key element of monitoring/diagnosing and caring for cancer patients: CTC and CAM counts have been deemed to be a very good measure of the progression of the illness, some papers (of many more) related to this subject below:
CAML study related to my previous post from the Journal of Clinical Oncology.
https://ascopubs.org/doi/abs/10.1200/JCO.2017...uppl.11503
Role of Circulating Tumor Cell (CTC) Monitoring in Evaluating Prognosis of Triple-Negative Breast Cancer Patients in China
ttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5493060/
The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper
https://www.sciencedirect.com/science/article...via%3Dihub
48 non-small cell lung cancer Patients Circulating Tumor Cell Assessment in Presumed Early Stage Non-Small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy: A Prospective Pilot Study
https://pubmed.ncbi.nlm.nih.gov/30244877/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912467/
For breast cancer, the article summarized the completed and ongoing clinical trials (as of 2019) using CTC number or phenotype for treatment decisions (7 studies).
https://www.medpagetoday.com/meetingcoverage/...lsmm/87147
Medpage article (June 2020) on Prostate cancer discussing a large phase III randomized clinical trial, SWOG S1216, a study run by the NCI Southwest Oncology Group.
As we all know, metastasis is responsible for a large percentage of mortality on Oncology.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597235/
The estimation is that 90% of deaths are from metastatic cancer. That is, if LL indeed can reduce CTCs and CAMLs we will have a substantial impact on clinical outcomes for patients (substantial might be an understatement).
The conclusion is clear: CTCs are a biomarker of overall survival rate (ORS). A CTC threshold of 5 cells per 7.5 ml defines to a great extent ORS in several types of cancers.
Most of oncology drugs objective is to extent ORS for patients. This defines the success (or lack off) of a therapy.
As a remainder from previous conferences:
Quote:VANCOUVER, Washington, Dec. 23, 2019 (GLOBE NEWSWIRE) -- CytoDyn Inc. (OTC.QB: CYDY), (“CytoDyn” or the “Company" , a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today continued promising clinical responses from its metastatic triple-negative breast (mTNBC) Phase1b/2 trial and its trial investigating leronlimab for the treatment of metastatic breast cancer (MBC).
Further data from the first mTNBC cancer patient continues to show no detectable circulating tumor cells (CTC) or putative metastatic tumor cells in the peripheral blood and additional reductions in CCR5 expression on cancer-associated cells at 11 weeks of treatment with leronlimab. Additional data in an emergency IND protocol involving one MBC patient demonstrated shrinkage of tumor (via MRI) after three weeks of treatment with leronlimab.
“In the first patient, we’re encouraged to see that after 11 weeks these additional data provide further preliminary evidence of efficacy, as demonstrated by sustained undetectable levels of CTCs and a reduction of cancer-associated macrophage like cells (CAMLs) ,” said Bruce Patterson, M.D., Chief Executive Officer of IncellDx. “Thus far, the data have been consistent with previous studies evaluating leronlimab as a long-term therapy for HIV+ patients, with no serious adverse effects reported in the mTNBC trial.”
CytoDyn’s second patient enrolled is a stage 4 MBC patient. The metastasis progressed to the liver, lung and brain. This patient was enrolled through an emergency IND. The patient was on Herceptin and Perjita for over 1.5 years. Herceptin is known to stop working after about 12 months, while Perjita is effective for approximately 1.5 years. This patient received her first injection of leronlimab on November 25, with one 700 mg dose each week.
Regarding the second patient, Nader Pourhassan, Ph.D., president and chief executive officer of CytoDyn, stated: “It is very exciting to see ongoing results that demonstrate leronlimab’s potential as a therapeutic option to treat patients with mTNBC and MBC with HER2+ condition. This second patient was enrolled in an emergency IND.”
Added Dr. Patterson, “The results from two subsequent scans of the metastatic lesions for this second patient demonstrated shrinkage of the tumors at both timepoints following the first leronlimab injection, reduction in brain edema, and remarkably, disappearance of several metastatic tumors.”
Dr. Pourhassan continued, “Due to these very promising clinical data, we feel that the 98% inhibition of metastasis shown by our animal studies may soon become a reality for many cancer patients throughout the world. We are cautiously optimistic and believe we have enough results in an unmet medical need population to justify filing for Breakthrough Therapy Designation in January 2020.”
So, we need as much information as we can get of the current status of the Cancer patients (from basket trial and otherwise). A reduction of counts means “we have a signal” as NP says. And a very strong one I might add. Reducing CTC 7 CAMS counts = OS extension (big time).
Are we still reducing CTCs ????. What is the status after several months (years) of treatment ???
Pleaaaaseeeee tell us …..
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