Julian Adams, PhD

Julian Adams, PhD, president, Research and Development, Infinity Pharmaceuticals, discusses the rationale behind the DUO trial.

In this phase III trial, IPI-145 is being compared with ofatumumab in patients with relapsed or refractory CLL or SLL.

This trial is being conducted based on high nodal responses seen in a phase I trial.

IPI-145 has elicited responses in patients with the 17p deletion, a group that typically has a poor prognosis.

Videos

The DUO Trial: IPI-145 vs Ofatumumab in Relapsed or Refractory CLL or SLL

Julian Adams, PhD, president, Research and Development, Infinity Pharmaceuticals, discusses the rationale for a phase II trial looking at IPI-145 for the treatment of patients with refractory indolent non-Hodgkin lymphoma. This trial, labeled DYNAMO, was presented at the 2014 ASCO Annual Meeting.

In the course of a phase I investigation of IPI-145, patients with indolent lymphoma were enrolled.

The overall response rate of this group was 73%. The complete response rate was 20%.

These results were compelling enough to enroll a single-arm study of 120 patients with refractory indolent non-Hodgkin lymphoma. The trial is ongoing.

Julian Adams, PhD, president, Research and Development, Infinity Pharmaceuticals, discusses the rationale for a phase II trial looking at IPI-145 for the treatment of patients with refractory indolent non-Hodgkin lymphoma.

The DYNAMO Trial: IPI-145 for Refractory Indolent Non-Hodgkin Lymphoma

Julian Adams, PhD, President, Research and Development, Infinity Pharmaceuticals, discusses PI3K inhibitors and chemotherapies for the treatment of hematologic malignancies.

Traditionally, patients are treated with chemotherapy and anti-CD20 therapies. Eventually, Adams says, patients relapse and are no longer responsive. A further challenge arises in that many of these patients are elderly and cannot tolerate aggressive chemotherapies.

Adams says that targeted therapies such as PI3K-delta and PI3K-gamma inhibitors will obviate the need for harsh therapies. With these therapies, physicians will be able to rescue patients from their chronic and aggressive diseases.

Traditionally, a patient with a hematologic malignancy will be treated with chemotherapy and anti-CD20 therapies

Many patients are elderly and cannot tolerate aggressive chemotherapies

With targeted therapies like PI3K-delta and PI3K-gamma inhibitors, the need for harsh therapies will be obviated

Julian Adams, PhD, from Infinity Pharmaceuticals, discusses PI3K inhibitors and chemotherapies for the treatment of hematologic malignancies.

An Overview of the Treatment of 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.

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

View all coverage from the 2013 ASCO Meeting

Julian Adams, PhD, President, Research and Development, Infinity Pharmaceuticals, describes a phase I trial of IPI-145, a potent inhibitor of PI3KEÎ´ and PI3K-Î³.

Julian Adams, PhD | Authors

Articles

The DUO Trial: IPI-145 vs Ofatumumab in Relapsed or Refractory CLL or SLL

The DYNAMO Trial: IPI-145 for Refractory Indolent Non-Hodgkin Lymphoma

An Overview of the Treatment of Hematologic Malignancies

The Phase I Trial of IPI-145 in Hematologic Malignancies