Semafore Pharmaceuticals Reports Encouraging Data on SF1126 in Relapsed and Refractory Myeloma

Strategic Insights -

Semafore Pharmaceuticals announced encouraging data from a Phase I dose-escalation trial of SF1126 in patients with relapsed and refractory myeloma. The novel small molecule inhibitor of PI3K and mTOR demonstrated significant suppression of the PI3K pathway in tumor cells at well-tolerated doses. The study is evaluating SF1126 administered as a 1.5 hour intravenous infusion given twice a week for four weeks on a 28 day cycle, with a total of 8 patients treated with escalating doses ranging from 90 to 1110 mg/m2 for a median of one cycle.

Key Takeaways:

  • SF1126, a dual PI3K-mTOR inhibitor, demonstrated significant suppression of the PI3K pathway in tumor cells at well-tolerated doses.
  • The study enrolled 8 patients with relapsed and refractory myeloma, who received escalating doses of SF1126 ranging from 90 to 1110 mg/m2 for a median of one cycle.
  • The most frequently occurring adverse events were nausea, allergic reaction, and vomiting, with no clinically significant changes in glucose or insulin levels reported at biologically active doses.
  • Pharmacodynamic analyses using serial bone marrow samples demonstrate substantial reductions in biomarkers of PI3K pathway activity in marrow plasma cells.
  • Pharmacokinetic analyses indicate that the maximal concentration and exposure of SF1126 increased with doses at 140 mg/m2 or higher, achieving exposures demonstrated to be efficacious in animal xenograft models of multiple myeloma.
  • One patient achieved stable disease as evidenced by urinary protein stabilization following a rapid rise prior to study initiation.
  • Semafore Pharmaceuticals plans to initiate combination trials of SF1126 with other active agents in myeloma in the near future.
  • The company has received capital commitments from existing shareholders to expand ongoing Phase I studies into B-cell malignancies, such as non-Hodgkins lymphoma (NHL) and chronic lymphocytic leukemia (CLL).

Statistics:

  • 8 patients enrolled in the Phase I dose-escalation trial of SF1126.
  • Escalating doses of SF1126 ranged from 90 to 1110 mg/m2 for a median of one cycle.
  • The most frequently occurring adverse events were nausea (6/8), allergic reaction (4/8), and vomiting (3/8).
  • No clinically significant changes in glucose or insulin levels were reported at biologically active doses.
  • Pharmacodynamic analyses using serial bone marrow samples demonstrate substantial reductions in biomarkers of PI3K pathway activity in marrow plasma cells in 7/8 patients.
  • Pharmacokinetic analyses indicate that the maximal concentration and exposure of SF1126 increased with doses at 140 mg/m2 or higher in 6/8 patients.

Sources:

  • Semafore Pharmaceuticals, Inc.
  • Blood Weekly editors
  • NewsRx.com