Infinity Pharmaceuticals, Inc. reported encouraging data from its ongoing Phase 1 study of IPI-145, its oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, in patients with relapsed/refractory T-cell lymphoma, a difficult to treat hematologic malignancy with few available treatment options. Preliminary data showed that IPI-145 is clinically active in patients with T-cell lymphoma, with an overall response rate of 38%, including one complete response and nine partial responses among 26 patients evaluable for response. These findings were reported during the 6th Annual T-Cell Lymphoma Forum being held from January 23 to 25, 2014, in San Francisco, CA.

Summary of Phase 1 Data of IPI-145 in T-Cell Lymphoma. The poster presentation, "Clinical activity of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-,, in patients with relapsed/refractory T-cell lymphoma: Preliminary results from an ongoing Phase 1 study," included 30 patients in the safety population, of which 26 were evaluable for clinical activity. Patients enrolled in the study had advanced disease, with a median of five prior systemic therapies (range: 1 to11) and a median of one month from last therapy to first dose on study (range: 0.2 to 12).

Clinical Activity: Treatment with IPI-145 in patients with T-cell lymphomas led to an overall response rate of 38%, including one complete response and nine partial responses among 26 patients evaluable for response. Among the 11 patients with peripheral T-cell lymphoma (PTCL) evaluable for activity, IPI-145 led to one complete response and five partial responses, for an overall response rate (ORR) of 55%. Among the 15 patients with cutaneous T-cell lymphoma (CTCL) evaluable for activity, IPI-145 led to four partial responses, for an ORR of 27%.

Stable disease was observed in seven patients with CTCL. The onset of activity was rapid, with a median time to response of 1.9 months (range: 1.5 to 2.7) for patients with PTCL and 2.4 months (range: 1.7 to 3.8) for patients with CTCL. The median number of treatment cycles for the 13 patients with PTCL was 2.2 (range: 0.5 to 8), and the median number of treatment cycles for the 17 patients with CTCL was 3.1 (range: 0.4 to 11).

Four patients with PTCL and three patients with CTCL remain on treatment. Safety and Pharmacodynamics: IPI-145 was generally well tolerated, with the majority of patients receiving IPI-145 dosed at 75 mg twice daily (BID). The most common Grade 3 side effects were increases in ALT or AST (two liver enzymes) (10 patients; 33%), rash (4 patients; 13%) and fatigue (3 patients; 10%).

One patient (3%) had Grade 4 ALT or AST increases. Data also showed that treatment with IPI-145 led to decreases in serum levels of cytokines and chemokines known to play important roles in lymphocyte trafficking and function, further supporting the rationale that inhibiting PI3K-delta and PI3K-gamma has the potential to provide a therapeutic benefit for T-cell lymphoma as well as other blood cancers.