Phase 3 Trial To Compare Carfilzomib and Velcade For Relapsed Multiple Myeloma – On Monday, Onyx Pharmaceuticals announced the start of a Phase 3 trial comparing the safety and efficacy of its investigational drug carfilzomib ^[1] (Kyprolis ^[2]) to that of Velcade ^[3] (bor­tez­o­mib). In particular, the trial will in­ves­ti­gate the efficacy and safety of car­filz­o­mib in com­bi­na­tion with dexamethasone ^[4] (Decadron) versus Velcade plus dexa­meth­a­sone in patients who have received one to three prior lines of ther­apy. Carfilzomib is in the same class of drugs as Velcade, known as proteasome inhibitors. It is cur­rently under review by the U.S. Food and Drug Administration for potential approval as a new treat­ment for myeloma (see related Beacon ^[5] news). For more in­­for­ma­tion, please see the Onyx Pharmaceuticals ^[6] press release and the clinical trial ^[7] description.

Phase 3 Trial Of MLN9708 Begins In Patients With Relapsed Or Refractory Myeloma – Millennium Pharmaceuticals, the com­pany that developed Velcade and markets the drug in the United States, announced last week the initiation of an inter­na­tional Phase 3 clinical trial of its investigational com­­pound MLN9708 ^[8] (ixazomib ^[9]) in patients with re­lapsed or refractory multiple myeloma. The study will in­ves­ti­gate the efficacy and safety of MLN9708 in com­bi­na­tion with Revlimid ^[10] (lena­lido­mide) and dexa­meth­a­sone. Like car­filz­o­mib and Velcade, MLN9708 is a proteasome inhibitor; however, it is admin­istered orally. In recent Phase 1/2 clinical trials, MLN9708 showed promising results as a single agent as well as in com­bi­na­tion with Revlimid and dexa­meth­a­sone in both newly diagnosed and re­lapsed/refractory myeloma patients (see related Beacon ^[11] news). For more in­­for­ma­tion, please see the Millennium ^[12] press release and the clinical trial ^[13] description.

Researchers Identify Potential Reason For Drug Resistance In Some High-Risk Multiple Myeloma Patients – Researchers from the United States and Singapore have found that a small molecule of RNA called ACA11 may be the reason for drug resistance in multiple myeloma patients with the chromosomal ab­nor­mal­ity t(4;14). Specifically, the researchers found that ACA11 was present in all the cancer cells of patients with t(4;14). As the amount of ACA11 increased, levels of oxidative stress that damage cells went down, protecting cancer cells from damage. As a result, the cancer cells were more resistant to chemotherapy. Patients with t(4;14), which is a translocation of a region of chromosome 4 to chromosome 14, are considered high-risk patients (see related Beacon ^[14] news). For more in­­for­ma­tion, please see the study in The Journal of Clinical Investigation ^[15] and the Washington University in St. Louis ^[16] press release.

Japanese Phase 1 Trial To Study Perifosine For Refractory Myeloma – The Canadian bio­tech com­pany Aeterna Zentaris announced last week that its partner in Japan, Yakult Honsha, has begun a Phase 1 clinical trial of perifosine ^[17] (KRX-0401) in multiple myeloma patients who are resistant to Velcade treat­ment. The study will evaluate the safety of  perifosine in com­bi­na­tion with Velcade and dexa­meth­a­sone in 18 patients. Perifosine is an orally admin­istered drug that belongs to a new class of anti-cancer drugs called “Akt inhibitors.” In the United States, perifosine in com­bi­na­tion with Velcade and dexa­meth­a­sone is in Phase 3 trials for multiple myeloma (see related Beacon ^[18] news). For more in­­for­ma­tion, please see the Aeterna Zentaris ^[19] press release.