Ian Flinn, MD, PhD, director of the hematologic malignancies program at Sarah Cannon Research Institute, discusses findings from a phase I study that explored monotherapy with the PI3K-gamma and delta inhibitor duvelisib (IPI-145) in patients with relapsed/refractory indolent non-Hodgkin lymphoma (iNHL).

The study enrolled 34 patients who received duvelisib across a variety of doses. At the dose selected for phase III studies, 25 mg twice daily, duvelisib demonstrated an overall response rate (ORR) of 72%, notes Flinn. Thirty-three percent of patients experienced a complete response (CR). Among patients specifically with follicular lymphoma (n = 13), the ORR was 69%, including a 38% CR rate.

The treatment is currently being explored in the phase II DYNAMO trial and the phase III DYNAMO+R trial for patients with NHL. DYNAMO will asses duvelisib as monotherapy and DYNAMO-R will combined the novel therapy with rituximab.

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Ian Flinn, MD, PhD, director of the hematologic malignancies program at Sarah Cannon Research Institute, discusses findings from a phase I study that explored monotherapy with the PI3K-gamma and delta inhibitor duvelisib (IPI-145) in patients with relapsed/refractory indolent non-Hodgkin lymphoma.

Dr. Ian Flinn Discusses Duvelisib Monotherapy in iNHL

Ian W. Flinn, MD, PhD, director, Hematologic Malignancies Research Program, Sarah Cannon Research Institute, discusses the DYNAMO Trial, which is looking at IPI-145 for the treatment of patients with refractory indolent non-Hodgkin lymphoma.

Flinn says this phase II trial enrolled patients who were no longer responding to rituximab or chemotherapy. There is currently no established therapy for these patients.

In this trial, all patients will receive IPI-145, an oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, as a single agent, Flinn says. Targeting PI3K-delta and PI3K-gamma may provide multiple opportunities to develop differentiated therapies for the treatment of blood cancers and inflammatory diseases.

The trial is ongoing and is currently accruing patients in the United States and the United Kingdom.  

Dr. Flinn Discusses the DYNAMO Trial

Ian W. Flinn, MD, PhD, director, Hematologic Malignancies Research Program, Sarah Cannon Research Institute, discusses IPI-145, an oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K- gamma.

Flinn says this agent builds on work that has been previously done with delta-specific PI3K inhibitors such as idelalisib. IPI-145 also picks up the gamma isoform, which may help treat other hematologic malignancies such as T cell lympohomas and more aggressive forms of lymphoma.

T cells are important in perpetuating the malignancy in lymphoma and CLL, Flinn says. Targeting the gamma isoform abrogates the protective effect of the microenvironment on the cancer cell.

Dr. Flinn Discusses IPI-145 as Potential Treatment for Hematologic Malignancies

Ian W. Flinn, MD, PhD, from the Sarah Cannon Research Institute, discusses the preliminary efficacy of IPI-145 in patients with chronic lymphocyic leukemia (CLL).

IPI-145 is a potent oral inhibitor PI3K-delta and -gamma that was examined in a phase I trial that enrolled 44 patients with relapsed or refractory CLL. Overall, there was a 47% overall response rate, as evaluated by modified IWCLL criteria, in a heavily pretreated population of patients with CLL, Flinn notes. Additionally, there was a 50% response rate even in patients with 17p deletions or TP53 mutation.

When considering the mild toxicity profile along with the efficacy, IPI-145 represents a very promising new treatment option, Flinn notes. As a result, IPI-145 will be further examined in a phase III trial in comparison to ofatumumab.

View more from the 2013 ASH Annual Meeting

Ian W. Flinn, MD, PhD

Articles

Dr. Ian Flinn Discusses Duvelisib Monotherapy in iNHL

Dr. Flinn Discusses the DYNAMO Trial

Dr. Flinn Discusses IPI-145 as Potential Treatment for Hematologic Malignancies

Dr. Flinn Discusses the Efficacy of IPI-145 in CLL