Friday, April 24, 2015

Copanlisib for Follicular Lymphoma

Last week (yes, I'm still catching up), the manufacturer of Copanlisib announced that it was expanding its clinical trials, with two new phase III trials for indolent lymphoma and one new phase II trial for DLBCL. This is good news (assuming enough people sign up for the trials, of course).

Lots to unpack here.

Copanlisib hasn't been in the news much, at least not the news that I have been reading.  First off, let us note that Copanlisib is a pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor. Kinase inhibitors are a type of treatment that has certainly been in the news lately for Follicular Lymphoma and other lymphomas. These are "pathway treatments" -- they don't attack the cancer cells directly, but block the pathways that help cancer cells develop, grow, and multiply. PI3K inhibitors work by blocking signalling pathways in cells. That is, before a cell can grow, it needs a signal from somewhere else down the pathway. Cancer cells get that signal, but keep on growing.  A PI3K inhibitor keeps that signal from reaching the cell. No signal, no growth. No growth, no cancer.

Now, there is another PI3K inhibitor already approved out there -- Idelalisib. From what I can tell, Idelalisib and Copanlisib will work through slightly different mechanisms, and will target slightly different pathways. Basically, kinases are proteins, and they come in different forms. Idelalisib targets the "delta" form of the protein, while Copanlisib shows activity against both the "delta" and "alpha" forms. So maybe there is a chance that they will work together, or compliment each other in some way.

Copanlisib has already shown some good activity in indolent lymphoma. At the ASH conference a few months ago, results from a phase II study showed that, in 33 patients with different types of NHL (including 16 with Follicular Lymphoma), all of whom had already been given several treatments, almost half had a response. For the Follicular Lymphoma patients, 1 had a Complete Response, 1 had an unconfirmed Complete Response, and 5 had Partial Responses, for an Overall Response of 47%. Not too bad.

Those same patients will be the target group for one of the phase III trials announced last week.

So, this is good news. Another potential arrow for the quiver, as they say -- another possible way of attacking this disease. But in a targeted manner.

Of course, we are still early in the process. As Karl from has pointed out before, we have lots of potential new treatments out there in various stages of the pipeline, and that is certainly something to cheer. But unless we get enough people who are willing to be a part of the clinical trials for those treatments, we won't really know just how effective they might be.

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