Clinical Trial - Selinexor (KPT-330) For MDS

Karyopharm is in phase 2 of a clinical trial studying Selinexor (KPT-330) in MDS patients. The question they’re asking: Can Selinexor improve blood counts and bone marrow function in MDS patients?

What is Selinexor? 

Selinexor is in a new class of drugs called Selective Inhibitors of Nuclear Export (SINE). Cancer cells, in order to grow and multiply, have to block tumor suppressing proteins (TSP’s). TSP’s need to be able to accumulate in the nucleus of a cell in order to function properly. These TSP’s are brought into the nucleus by carrier proteins called importins. They are then carried out of the nucleus into the cytoplasm by another type of carrier protein called exportins. 

Imagine TSP’s as workers hired to fight cancer. They need a shuttle to get to work in the nucleus of the cell and then need a ride out after. Importins and exportins are the shuttles bringing the cancer fighters into the nucleus to do their job and then later, out of the nucleus. One problem with cancer cells, is that they want the cancer fighters to fail at their job by leaving the nucleus before they can do anything to stop the cancer from growing. To try to stop them from being successful, cancer cells hire a bunch of extra exportin shuttles to try to get the cancer fighters out of the nucleus before they can do any work. One exportin in specific, called XPO1 is the shuttle most often hired to carry TSP's out of the nucleus. In fact, research has shown that XPO1 is over expressed by 2-4 times in cancer cells. 

Selinexor targets this problematic exportin, XPO1, which is responsible for carrying most TSP’s out of the nucleus. With XPO1 blocked, TSP’s are able to stay in the nucleus and more efficiently work together to stop the cancer from growing. Phase 1 trials with Selinexor across cancer types have shown evidence of anti-tumor behavior which has prompted its study in MDS.

Selinexor in MDS Trial

In the Karyopharm study on Selinexor in MDS, researchers are aiming to see if this drug with success in Multiple Myeloma, another blood cancer, can also help MDS patients. This phase of the trial (phase 2) is primarily focused on finding out if the drug is tolerable to MDS patients and if results show indication that the drug will improve patients blood counts and bone marrow function. 

Recruitment for this phase of the trial is completed, with 25 MDS patients who are refractory to hypomethylating agents. Patients recieve Selinexor orally, at the starting dose of 60mg twice a week for 2 weeks followed by a week off with no therapy. The first round of results were posted in March of 2022, with no serious adverse events reported. Other adverse events like nausea and fatigue were reported. 

Looking Forward

There is still a ways to go before Selinexor could be FDA approved for use in treating MDS patients, however the possibility of a new treatment option on the horizon for MDS patients is exciting! Here at HealthTree we will be following this trial and will continue to report on its findings and progress.