Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) today announced new data from its ongoing Phase 1, open-label, dose-escalation trial of IPI-145, the company's potent, oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, in patients with advanced hematologic malignancies. Preliminary data from the study showed that IPI-145 was well tolerated to date and clinically active in patients with both B-cell and T-cell malignancies, including chronic lymphocytic leukemia, indolent non-Hodgkin's lymphoma, mantle cell lymphoma, Hodgkin's lymphoma and T-cell lymphoma. These findings were presented today at the 54th Annual Meeting of the American Society for Hematology (ASH) in Atlanta, Georgia.
"Data from this Phase 1 trial of IPI-145 show good tolerability and rapid clinical responses across a broad spectrum of difficult-to-treat hematologic malignancies," commented Ian Flinn, M.D., Ph.D., director, hematologic malignancies research program, Sarah Cannon Research Institute, and an investigator for the trial. "These data are especially encouraging considering that the dose escalation phase of this study is still ongoing, so we look forward to the further clinical evaluation of IPI-145."
"These results reinforce our enthusiasm for IPI-145. We believe that the potency and activity of IPI-145 against both PI3K-delta and PI3K-gamma contribute to its potential to become the best-in-class PI3K inhibitor for the treatment of hematologic malignancies," stated Julian Adams, Ph.D., president of R&D at Infinity. "In particular, we believe the data presented today at ASH are the first to show activity against T-cell lymphoma by a PI3K inhibitor. We look forward to expanding the trial in additional cohorts of patients at or below the maximum tolerated dose."
IPI-145 Data Presented at ASH
The poster, "Clinical safety and activity in a Phase 1 trial of IPI-145, a potent inhibitor of phosphoinositide-3-kinase (PI3K)-delta,gamma in patients with advanced hematologic malignancies" (Abstract #3663), includes 55 patients evaluable for tolerability and 41 patients evaluable for clinical activity as of the November 20, 2012, data cutoff.
Tolerability and Pharmacokinetics
The Phase 1, open-label, dose-escalation trial of IPI-145 is designed to evaluate the safety, pharmacokinetics (PK) and clinical activity of IPI-145 administered orally twice daily (BID) in patients with advanced hematologic malignancies. The maximum tolerated dose has not been reached at doses up to 75 mg BID. Thus, the trial is ongoing, and patients are now being enrolled in a dose-escalation cohort evaluating IPI-145 at a dose of 100 mg BID.
Data presented today showed that IPI-145 was well tolerated to date, and there have been no dose-related trends in adverse events. The most frequent Grade 3 and Grade 4 adverse events were cytopenias and liver enzyme elevations, which were managed by dose interruption and dose reduction. Of the 55 patients evaluable for tolerability, three (5 percent of) patients discontinued treatment due to an adverse event. Sixty-seven percent of all patients remain on study, and 90 percent of patients who did not experience progressive disease after two cycles remain on study.
Data also showed that IPI-145 is rapidly absorbed and demonstrates a linear PK profile through all dose levels analyzed thus far. The PK data suggest that IPI-145 completely inhibits PI3K-delta, with increasing suppression of PI3K-gamma at doses greater than or equal to 25 mg BID.
IPI-145 showed broad activity in patients with both B-cell and T-cell malignancies, including partial responses or complete responses in patients with chronic lymphocytic leukemia, indolent non-Hodgkin's lymphoma, mantle cell lymphoma, Hodgkin's lymphoma and T-cell lymphoma. Onset of activity appeared to be rapid, as evidenced by the median time to response (table below). Additionally, clinical activity reported for 16 of 19 responders occurred within the first two cycles of treatment.
Clinical responses as of the November 20, 2012, data cutoff were as follows:
iNHL (indolent non-Hodgkin's lymphoma), CLL/SLL (chronic lymphocytic leukemia/small lymphocytic lymphoma), aNHL (aggressive non-Hodgkin's lymphoma, including diffuse large B-cell lymphoma (DLBCL)), MCL (mantle cell lymphoma), MM (multiple myeloma), HL (Hodgkin's lymphoma)
The Phase 1 study poster is being presented in the Georgia World Congress Center, Hall B1-B2, and may also be found in the Publications Archive on Infinity's website http://www.infi.com/product-candidates-publications.asp.
Additional Program Updates
Infinity today also provided the following updates related to its PI3K program:
Continued progress anticipated in Phase 1 dose-escalation trial of IPI-145: Based on data observed to date, Infinity expects to expand its ongoing Phase 1 study of IPI-145 in up to five cohorts based on responses observed during the dose-escalation phase at or below the maximum tolerated dose.
Update on Phase 2a trial in asthma: Infinity is currently conducting a Phase 2a, randomized, double-blind, placebo-controlled trial of IPI-145 in approximately 30 patients with mild, allergic asthma. Endpoints of this multi-dose, two-way crossover study include safety, pharmacokinetics and FEV1, a standard measure of lung function. The company expects to provide an update on this study in 2013.
Planning for Phase 2 trial in RA continuing: In November 2012, Infinity presented data from its completed Phase 1 trial of IPI-145 in healthy subjects. Infinity believes that these data, combined with preclinical data in multiple animal models of rheumatoid arthritis (RA), support Phase 2 development in this indication. Infinity expects to begin a Phase 2 trial of IPI-145 in patients with moderate to severe RA in the first half of 2013.
Follow-on PI3K inhibitor expected: Infinity is developing a portfolio of novel PI3K-delta and/or PI3K-gamma inhibitors. The company expects to announce its first follow-on PI3K development candidate by the end of this year and is planning to complete nonclinical studies by the end of 2013, which are designed to enable Phase 1 development.