The Phase I Trial of IPI-145 in Hematologic Malignancies

Julian Adams, PhD, President, Research and Development, Infinity Pharmaceuticals, describes a phase I trial of IPI-145, a potent inhibitor of PI3K-delta and PI3K-gamma.

IPI-145 showed remarkable activity in hematologic malignancies in a phase I trial. At the 2013 American Society of Clinical Oncology Meeting, it was announced that a phase II trial would take place, looking to accrue 120 patients with indolent non-Hodgkin lymphoma in the relapsed/refractory setting.

The phase I trial had two portions. First, the dose-escalation phase enrolled 33 patients between 8mg and 100mg, defining 75mg as the maximum-tolerated dose. In the second phase, 25mg and 75mg cohorts showed potent activity in blocking phosphorylation of AKT and downstream chemokine and cytokines. Both doses have shown a great deal of activity across a broad spectrum of hematologic malignancies.

Data are still maturing in this trial, Adams notes, but responses were observed of about 68% in indolent non-Hodgkin lymphoma. In chronic lymphocytic leukemia (CLL), a 55% response rate was observed, with an additional 35% nodal response. The trial is not as far along in T-cell malignancies, but good responses have been seen in patients with Sezary syndrome and patients with peripheral T-cell lymphoma.

Clinical Pearls

IPI-145 has been generally well tolerated in this space, with no dose-related adverse events. Sporadic adverse events have been observed due to comorbidities associated with CLL and lymphoma, though this is to be expected, Adams says.

• IPI-145 is a potent inhibitor of PI3K-delta and PI3K-gamma
• In a phase I trial, the drug showed activity across a broad spectrum of hematologic malignancies
• There was about a 68% response rate in an early assessment of indolent non-Hodgkin lymphoma and 55% in chronic lymphocytic leukemia
• IPI-145 has been generally well tolerated by patients, with no dose-related adverse events

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