Ignyta’s RXDX-106 can restore the body’s immune-system response against several types of tumors and work with immune checkpoint inhibitors to kill tumor cells, according to a company presentation at the American Association for Cancer Research annual meeting.
RXDX-106, which is a small-molecule inhibitor, can block the TAM family of receptor tyrosine kinases (RTKs), Ignyta said. These cell-surface receptors regulate critical processes in normal and cancer cells, including growth and survival.
Ignyta said RXDX-106 recruited to tumors, and activated, immune-system T-cells that overrode tumor macrophages’ immunosuppressive behavior. The bottom line was that the therapy inhibited tumor growth, the company said. The study also indicated that RXDX-106 can work in synergy with immune checkpoint inhibitors to eliminate tumor cells.
The company’s poster-session presentation was titled “Immuno-oncological efficacy of RXDX-106, a novel, selective and potent small molecule TAM (TYRO3, AXL, MER) inhibitor.”
“We continue to be excited by our pipeline progress, including the emerging preclinical profile of RXDX-106 and its potential to restore and enhance a patient’s immune response to cancer,” Jonathan Lim, chairman and CEO of Ignyta, said in a press release. “Our preclinical data confirm TAM receptors as novel immuno-oncologic targets in the fight against cancer, highlighting both the single agent activity of RXDX-106, as well as a possible synergistic effect when combined with other immuno-oncology treatments such as checkpoint inhibitors.”
TAM RTKs have been implicated in the onset and progression of many cancers. Over-expression of the proteins is associated with resistance to treatment and with cancer cells spreading to other parts of the body.
RXDX-106 displayed anti-tumor activity in mouse models of colon cancer, according to the Ignyta study. But the activity was seen only in mice with a fully functional immune system. This suggested that the drug requires a functional immune system to exert its effects.
That makes sense because TAM RTKs help cancer cells evade the immune system’s surveillance arm, which detects cancer cells.
The findings also revealed that RXDX-106 modulated the tumor microenvironment, starting with increasing the number of tumor-infiltrating lymphocytes, and activating them. It also increased the number of anti-tumor macrophages.
In addition, RXDX-106 led to an increase in the expression of PD-1, which tumor cells usually hijack so the immune system can’t recognize them. The team found that inhibiting the PD-1 molecule in conjunction with RXDX-106 further inhibited tumor growth in mouse models of breast and colon cancer, compared with RXDX-106 by itself.
Similar findings were seen when the team combined RXDX-106 with an immune checkpoint inhibitor that targeted the CTLA-4 molecule.
“The unique mechanism of activating both innate and acquired immunity by RXDX-106, and the compelling preclinical data in cell line and syngeneic models, support the clinical development of RXDX-106 in a wide variety of cancers,” the researcher wrote.