A Phase 1/2 Study of Oral LOXO-305 in Patients With Previously Treated CLL offers an option of a novel agent that non-covalently blocks BTK.
Ibrutinib has revolutionized the treatment of CLL but resistance can develop when the pocket (most commonly C-481) on BTK molecule where it binds mutates leading to its inability to block the B cell receptor (BCR). That allows BCR to restart its signaling to the CLL cells to grow and return to its protective microenvironment. That ultimately leads to disease progression. LOXO-305 binds differently and so should work whether or not the BTK binding site is normal (wild type) or has mutated (C-481), in theory decreasing the chances of developing resistance. LOXO-305 may also be a more selective BTK inhibitor, blocking fewer other pathways. Ibrutinib works great for most patients, but disease progression and drug intolerance are the reasons why patients do stop taking it.
This trial is open to any CLL patients who have had 2 or more prior therapies and may include patients who had progressed on ibrutinib. Sites are now recruiting in Boston, Sarasota, Nashville, Chapel Hill, Houston, New York City, Seattle and Australia.
The only way treatments keep improving CLL therapies is by brave patients enrolling in clinical trials and this is one worth discussing with your treatment team if you have had at least two prior therapies for your CLL.
Disclaimer: Please carefully review this or any clinical trial or therapy decision with your treatment team. The CLL Society wants you to be informed of all your treatment options but does not endorse any particular trial or therapy, including this one.
July 9, 2019