Semafore's SF1126 peptidic prodrug demonstrates clinical activity in chronic lymphocytic leukemia

Published on June 22, 2010 at 2:09 AM · No Comments

Semafore Pharmaceuticals today announced the presentation of preliminary clinical data demonstrating that SF1126 has clinical activity in chronic lymphocytic leukemia (CLL). SF1126 is a novel peptidic prodrug that converts to LY294002, one of the most widely studied small molecule inhibitors of both phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR). The results were presented at Cambridge Healthtech Institute's 8th Annual Next-Gen Kinase Inhibitors Oncology & Beyond Conference being held June 21-23, 2010, in Cambridge, Massachusetts.

“This provided a rationale to clinically explore the therapeutic activity of pan-PI3K inhibition with SF1126. While early, we are encouraged by the observed pharmacodynamic and clinical activity of SF1126 in two CLL patients, in addition to more mature data from solid tumor patients.”

"Recent data demonstrate that pan-PI3K inhibition may have desirable effects on chemotaxis and proliferation inhibition in CLL cells over delta isoform-selective PI3K inhibition," Daruka Mahadevan, M.D. Ph.D., Director, Phase I Program, Arizona Cancer Center. "This provided a rationale to clinically explore the therapeutic activity of pan-PI3K inhibition with SF1126. While early, we are encouraged by the observed pharmacodynamic and clinical activity of SF1126 in two CLL patients, in addition to more mature data from solid tumor patients."

Poster Title - "Update on the Novel Prodrug Dual mTOR-PI3K Inhibitor SF1126"

Solid Tumors

In an ongoing phase I dose escalation study in patients with solid tumors, SF1126 is administered twice per week on days one and four by a 90-minute intravenous infusion in cycles consisting of 4 weeks. To date 19 of 33 (58%) evaluable patients showed stable disease as best response with a median duration of 13 weeks (range 8 to +64) and a mean duration of about 19 weeks. Of particular note are three patients with stable disease for six months or longer, including a renal cell carcinoma patient previously resistant to the mTOR inhibitor temsirolimus with stable disease for 64 weeks that is still on study representing possible evidence of abrogating resistance to mTORC1 inhibition.

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