DCC-3014

DCC-3014 is an orally administered, potent and highly selective inhibitor of CSF1R. DCC-3014 was designed to selectively bind to the unique switch pocket in CSF1R. It has greater than 100-fold selectivity for CSF1R over other human kinases. CSF1R controls the differentiation and function of macrophages, a type of white blood cell that engulfs and digests cellular debris, foreign substances, microbes and cancer cells. These macrophages are also programmed to either activate the immune system to fight a cancer (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), have been shown to infiltrate certain tumors including cancers of the breast, cervix, pancreas, bladder and brain where poor prognosis correlates with the density of these TAMs. Tumors induce TAMs to suppress a natural immune response mediated by cytotoxic T-cells, a type of lymphocyte that would otherwise eradicate the tumor; a process known as macrophage checkpoints.

Tumor Type Target Status Retained Rights
Solid Tumors:
Monotherapy
Combo with Chemo
CSF1R inhibitor Phase 1 Trial – Ongoing Worldwide

Rationale for DCC-3014 in Solid Tumors:

The activity of DCC-3014 was evaluated in a colorectal cancer model. 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 or anti-PD1 antibody treatment alone.

Based on these findings, Deciphera has advanced DCC-3014 into a Phase 1 clinical in patients with advanced malignancies where TAMs are known or suspected to contribute to the growth and spread of the cancer.

Deciphera Immune Targeting

Kinases direct cell signaling activity to control cellular processes and are regulated by switches to adopt active or inactive kinase states.