How will the decreases in circulating tumor associated cells help patients with metastatic breast cancer? The Other clinical trial looked at circulating tumor associated cells to look at progression-free survival, overall survival. In our pooled analysis of all of our Bria-IMT trials to date where we had done these analyses, we’ve been collaborating with Creative Microtech, Dan Adams is the first author on this poster, and they have developed a very interesting biomark called Cancer Associated Macrophage Like Cells, abbreviated CAMLs, and I’m sure many of you are familiar with circulating tumor cells as a biomarker for patients, especially with advanced cancer. The group at Creative has discovered this other cell type, which has basically phenotypic markers of macrophage.
But they’re very large and they contain several nuclei, which are have been shown to be derived from the cancer cells themselves. So these are basically macrophages that have eaten cancer cells, presumably in the microenvironment of the tumor, and then have broken off and gotten into the circulation.
And so we looked at these cancer associated macrophage like cells and circulating tumor cells as a potential marker for both progression-free survival and for overall survival in our combined monotherapy and combination therapy experience.
And there’s a few things that popped out here, one was that in patients who had a high versus low CAMLs at baseline the progression-free survival and the overall survival was not necessarily very good. But in those who had decreases in CTCs or CAMLs. During our study, we saw a marked prolongation in both progression-free survival and in overall survival as well.
What is interesting about the CAMLs Biomarker?
This poster will be posted on our website, so you can take a look at that. We think that this is a very interesting biomarker going forward for as we continue to collaborate. With the people that create microtech. And our hazard ratios really are quite astounding here for some of these groups, 11.9 for decreases in circulating tumor cells or CAMLs (T-cells) compared to those who have increases.
And that applies to progression-free survival and for overall survival as even just in the monotherapy study it’s a hazard ratio of 20. So you can see that this is a very potentially powerful biomarker to help us differentiate those patients who are going to do well in our study as opposed to those who do not do as well.
And the biomarker was measured, I believe, after the third cycle of therapy in this analysis. So a very good way of gauging whether or not the patients are going to do well on our therapy.
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7 key takeaways from the SV-BR-1-GM Clinical Trial
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An exploratory post-hoc data for patients with metastatic breast cancer (MBC) treated with the SV-BR-1-GM regimen (SV) alone (NCT03066947) and in combination (CO) with immune checkpoint inhibitors (ICIs) (NCT03328026).
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SV comprises cyclophosphamide 300 mg/m2 i.v. 48-72 hours prior to SV-BR-1-GM (20 x 106 cells) intradermally, then by interferon-alpha-2b on days 2 and 4 at the SV-BR-1-GM inoculation sites. In NCT03066947, SV was administered every 2 weeks for 3 cycles and thereafter monthly, but in NCT033226, SV was administered every 3 weeks in combination with PD-1 inhibitors. The treatment was continued until progression of the disease or severe toxicity.
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V-BR-1-GM is a GM-CSF-expressing breast cancer cell line exhibiting antigen presentation cell (APC) characteristics due to the production of many immunomodulatory molecules, such as MHC-I (HLA-A, B, and C) and MHC-II (HLA-DRB3 & -DRA). Initial findings from patients treated with irradiated SV-BR-1-GM cells, low dose cyclophosphamide, and local IFN indicate that patients who match SV-BR-1-GM at least at one HLA allele are more likely to have clinical benefit.
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There were 2 grade 4 adverse events that were not treatment-related: worsening pleural effusion and changed mental status. Patients with matched HLA and the delayed-type hypersensitivity skin test, peripheral blood circulating tumor cells, and cancer-associated macrophages exhibited a significant improvement in PFS.
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Multiple subtypes of BC shown clinical advantages, notably in individuals with HR+ illness undergoing combination therapy. Currently, a Phase 2 clinical investigation is evaluating the efficacy of SV-BR-1-GM in combination with ICIs.
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Using flow cytometry and DNA sequencing, the lack of HLA-A and HLA-DRB3 expression was confirmed.
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Produces antigens (proteins made by breast cancer cells). GM-CSF is a protein that, when secreted, augments the immunological response. Antigens are “presented” to CD4+ and CD8+ T-cells, which are known to destroy tumors. Additionally boosts cancer-fighting T-cells directly, therefore enhancing the response.
William V. Williams, MD, FRCP – About The Author, Credentials, and Affiliations
Dr. Williams is an accomplished biopharmaceutical executive with more than 35 years of business and academic experience, including extensive clinical management in international pharmaceutical companies. Dr. Williams has served as President and CEO of BriaCell Therapeutics Corporation since October 2016. Previously, Dr. Williams served as Incyte Corporation’s vice president of exploratory development from 2005 to 2016.
He assisted the clinical introduction of approximately 20 drugs, including ruxolitinib (Jakafi) and baricitinib (Olumiant). As GlaxoSmithKline’s vice president of clinical pharmacology and experimental medicine, Dr. Williams examined several compounds in clinical studies pertaining to various therapeutic fields. A variety of oncology medications, including Bexxar (lymphoma), Hycamtin (ovarian cancer), and Navelbine (non-small cell lung cancer), as well as ibandronate (Boniva) for osteoporosis, received new or supplemental drug authorizations with his assistance.
As Head of Rheumatology Research at the University of Pennsylvania, he oversaw a substantial research program in receptor biology, cooperated with David B. Weiner, PhD to produce DNA vaccines, and was able to introduce innovative DNA vaccines for the treatment of cutaneous T cell lymphoma into the clinic. Dr. Williams obtained a Bachelor of Science in Chemistry and Biotechnology from MIT and a Doctor of Medicine from Tufts School of Medicine.
In the molecular immunology laboratory of Mark I. Greene, MD, PhD, FRCP, at the University of Pennsylvania, he established unique methodologies for the design of bioactive peptides and collaborated on the study of the (cell) activation of the p185/Human epidermal growth factor receptor 2 (HER2) receptor. HER-2 is a protein known to stimulate the development of cancer cells. Dr. Williams is the author of over 130 peer-reviewed papers, over 15 patents, and multiple Investigational New Drug Applications (INDs) and New Drug Applications (NDAs).