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Abstract 8546: A PHASE II TRIAL OF THE NOVEL ORAL AKT INHIBITOR PERIFOSINE(KRX-0401) IN RELAPSED AND/OR REFRACTORY WALDENSTROMS MACROGLOBULINEMIA (WM).
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Thirty-seven patients (median age 65 yrs) with advanced WM (76% had atleast two prior treatments) were enrolled, with most patients (>75%)previously treated with at least one course of therapy on rituximab. Allpatients were scheduled to receive 150 mg of perifosine daily in a 28 daycycle for at least 6 cycles. Toxicities were generally well managed andtolerated with Grade 1 & 2 GI related toxicities occurring in 30% of thepatients. Thirty-six patients were evaluable for response, assessed bycriteria established at the second consensus panel for WM, with results asfollows:
11/36 patients remain on treatment and the median Time to Progression(TTP) has not been reached (8 cycles with a range of 2 - 17+). In summary,the investigators conclude that single agent perifosine showed encouragingactivity with manageable toxicity in patients with relapsed/refractoryWaldenstroms macroglobulinemia. An overall response rate of 33% (CR + PR +MR) was reported with an additional 61% of patients achieving stable disease(SD).
"The phase 2 data presented today further confirms pre-clinical resultssuggesting the promising activity of perifosine in Waldenstrom'smacroglobulinemia," stated Dr. Ghobrial. "We are encouraged by the activity ofsingle agent perifosine in the treatment of patients with advancedWaldenstrom's macroglobulinemia, and the manageable toxicity profile seen todate.
Michael Weiss, CEO of Keryx Biopharmaceuticals, commented "We areencouraged by this new data for perifosine, which continues to show activityacross multiple forms of cancer. There is no FDA approved agent for thetreatment of Waldenstroms macroglobulinemia and we believe that perifosine mayoffer a novel treatment option for these patients. We look forward tocontinuing to explore the potential for perifosine in the treatment ofWaldenstroms macroglobulinemia as well as several other cancers, includingmultiple myeloma, renal cell carcinoma and brain cancer, both as a singleagent and in combination with other novel agents."
Copies of the posters are available by request to Keryx Biopharmaceuticals.
KRX-0401 (Perifosine) Mechanism of Action and Profile
KRX-0401 (Perifosine) is a novel, potentially first-in-class, oralanti-cancer agent that modulates Akt and a number of other key signaltransduction pathways, including the JNK and MAPK pathways, all of which arepathways associated with programmed cell death, cell growth, celldifferentiation and cell survival. The effects of perifosine on Akt are ofparticular interest because of the importance of this pathway in thedevelopment of most cancers, the evidence that it is often activated in tumorsthat are resistant to other forms of anticancer therapy, and the difficultyencountered thus far in the discovery of drugs that will inhibit this pathwaywithout causing excessive toxicity. High levels of activated Akt (pAkt) areseen frequently in many types of cancer and have been correlated with poorprognosis in patients with soft-tissue sarcoma, gastric, hepatocellular,endometrial, prostate, renal cell, head and neck cancers and hematologicalmalignancies
