New Study Hints at Promise of Small Molecule Inhibitors Against Lymphomas

U.S. researchers presented findings from a large Phase I trial at the annual meeting of the American Society of Hematology that explores a new, emerging class of drugs for B-cell cancers called small molecule inhibitors.

As more and more labs work on drugs that target proteins on the surface of tumor cells and use them as treatment targets, some Tennessee researchers are working on drugs that work in a different manner: from the inside of the cell outward.

And to boot, they come in pill form.

Blocking tumor activity

Investigators explored the safety and efficacy of an investigational small molecule inhibitor known as IPI-145. This inhibitor is designed to block the activity of phosphoinositide-3-kinase (PI3K), an enzyme responsible for CLL tumor cell signaling.

Researchers recruited 193 patients with an average age of 67, including more than 50 patients with treatment refractory CLL into a Phase I trial, seeking to determine the maximum tolerated dose of IPI-145.

IPI-145 demonstrated anti-tumor activity in patients with refractory disease at all doses studied. It also showed activity in about half of the patients who were found to have a mutated version of p53, the tumor suppressor gene that, when mutated, makes the disease very difficult to treat.

A valuable new treatment

Said Ian Flinn, M.D., Ph.D., of Sarah Cannon Research Institute in Nashville, Tenn., and the lead author of the study:

Our study results suggest that IPI-145 may lend itself well to long-term therapy of patients with CLL. While it has a well-tolerated profile similar to other drugs in its class – it may actually be more potent, which could contribute to its value for patients with relapsed or refractory disease in particular.

Next up for investigators will be a randomized, double-blind Phase II or III trial.

Source: ASH 2013

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