DCC-3014 is an investigational orally administered, potent and highly selective inhibitor of CSF1R. DCC-3014 was designed to selectively bind to the CSF1R switch pocket. DCC-3014 has greater than 100-fold selectivity for CSF1R over the closely related kinases FLT3, KIT, PDGFRα, PDGFRß and VEGFR2 and has an even greater selectivity for CSF1R over approximately 300 other human kinases. CSF1R is believed to control the differentiation and function of macrophages, a type of white blood cell that is programmed to either activate the immune system to fight cancer cells (so-called M1 macrophages) or programmed to inactivate the immune system and promote tumor growth (so-called M2 macrophages). Pro-tumoral M2 macrophages, also known as Tumor Associated Macrophages (TAMs), infiltrate certain tumors suppressing a natural immune response that would otherwise eradicate the tumor; a process known as macrophage checkpoints. In preclinical animal studies, DCC-3014 reduced these pro-tumoral M2 macrophages, inhibiting this immunosuppressive macrophage checkpoint.
DCC-3014 is in clinical development for the treatment of solid tumors as monotherapy.
DCC-3014 in Solid Tumors:
The activity of DCC-3014 was evaluated in a mouse model of colorectal cancer. In this model, tumor growth leads to metastasis, and the model is also responsive to an emerging class of therapies known as anti-PD1 antibodies. The activity of DCC-3014 was evaluated on its own and in combination with an anti-PD1 antibody. In this preclinical disease model, the inhibiting effect of DCC-3014, in combination with an anti-PD1 antibody, was greater than that of vehicle control, control antibody oranti-PD1 antibody treatment alone.
Based on these findings, Deciphera has advanced DCC-3014 into a Phase 1 clinical study in patients with advanced malignancies where TAMs are known or suspected to contribute to the growth and spread of the cancer and is planning to expand this study to include patients with Tenosynovial Giant Cell Tumors (TGCT).
Further information on the DCC-3014 are available as follows:
Press Release here»
In addition, further information regarding DCC-3014 and Deciphera’s pipeline is available in the most recent corporate presentation here »
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