16 Jul AACR: Fusion Protein SO-C101 With Pembro in Adult Patients With Advanced/Metastatic Solid Tumors
MedicalResearch.com Interview with:
Radek Spisek MD PhD
Charles University in Prague
MedicalResearch.com: What is the background for this study?
Response: Immune cytokine IL-15 is a highly promising immuno-oncology target that mobilizes the two most important cell types driving anti-cancer immune responses: cytotoxic T cells and natural killer (NK) cells. Stimulating IL-15 receptors on these cells represents a potent and complementary mechanism to existing cancer treatments, such as PD-1 checkpoint inhibitors or monoclonal antibodies.
Sotio is developing an IL-15 superagonist, SO-C101, as a potent immunotherapy for patients with cancer. This study examined SO-C101 in multiple tumor mouse models alone and in combination with PD-1 inhibition.
MedicalResearch.com: What are the main findings? What are the challenges in safely dosing IL-15?
Response: These preclinical data demonstrate the importance of both cytotoxic T cells and NK cells for the anti-tumor activity of SO-C101. They highlight the ability of SO-C101 to reduce and prevent tumor growth in multiple mouse models through the activation and expansion of these two immune cell types when given as a monotherapy and in combination with PD-1 inhibitors. Key findings include the ability for SO-C101 to decrease the rate of tumor growth in lung and prostate cancer models while inducing proliferation of immune cells in the tumor, lymph nodes and spleen. Besides increasing the infiltration of the tumor tissue by CD8 T cells and NK cells, SO-C101 also increases the expression of PD1 on T cells thus providing the target for anti PD-1 therapy. In combination with PD-1 inhibition, SO-C101 prevents tumor development in a prostate cancer mouse model and induces long term antitumor immunity.
Binding specificity to IL-15beta gamma receptors on NK and cytotoxic T cells is crucial for safely dosing an IL-15 superagonist such as SO-C101. For example, unwanted binding to IL-2 alpha beta gamma receptors on endothelial cells can lead to severe adverse events, such as vascular leak syndrome. SO-C101 has been designed so it uniquely targets NK cells and CD8 T cells and it does not bind to receptors located on unwanted cell types including regulatory T cells and lung endothelial cells. To date, SO-C101 has demonstrated a favorable toxicology profile in mice as well as a strong safety profile and biological activity in SOTIO’s ongoing Phase 1/1b trial.
MedicalResearch.com: What should readers take away from your report?
Response: This report further demonstrates that IL-15 is a promising immuno-oncology target, as well as highlights the cancer immunotherapy potential of an IL-15 superagonist such as SO-C101 that binds selectively to NK and cytotoxic T cells. These preclinical data support the continued development of SO-C101.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: These preclinical data demonstrate the importance of conducting clinical studies with SO-C101 and encourage its development in combination with therapeutic modalities with a complimentary mechanism of action such as checkpoint inhibitors or monoclonal antibodies. SOTIO is currently on this path, with an ongoing Phase 1/1b dose finding study examining SO-C101 both as a monotherapy and in combination with the PD-1 inhibitor pembrolizumab in patients with metastatic solid tumors.
MedicalResearch.com: Is there anything else you would like to add?
Response: We look forward to completing the monotherapy arm of our Phase 1/1b dose finding study in advanced solid tumors before the end of 2020. We also look forward to initiating dose escalation in combination with pembrolizumab in summer 2020.
Citation: AACR 2020
Study of SO-C101 and SO-C101in Combination With Pembro in Adult Patients With Advanced/Metastatic Solid Tumors
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