This article is more than 5 years old. Information may no longer be current.
Oral PI3K inhibitor demonstrates activity in CLL
NEW ORLEANS — IPI-145, a new oral, potent PI3K inhibitor, appeared well tolerated and showed clinical activity in patients with chronic lymphocytic leukemia, including those with relapsed or refractory disease, according to preliminary findings presented at the ASH Annual Meeting and Exposition.
Ian W. Flinn, MD, PhD, of the Sarah Cannon Research Institute in Nashville, and colleagues assessed twice-daily 25 mg IPI-145 (Infinity Pharmaceuticals) in 15 treatment-naive patients, as well as twice-daily 25 mg (n=28) and 75 mg (n=24) doses in patients with relapsed, refractory CLL.
Ian W. Flinn
They then evaluated the safety, maximum tolerated dose, pharmacokinetics, pharmacodynamics and activity of orally administered twice-daily IPI-145 (dose range, 8 mg to 75 mg) in 28-day cycles.
Flinn and colleagues reported an overall response rate of 48%, with one complete remission. They observed clinical activity in patients with relapsed/refractory disease (median age, 67 years; 77% men) at all doses.
“This is emerging data that supports continued development of IPI-145 in patients with CLL and other hematologic malignancies,” Flinn said during a press conference. “While it has a well-tolerated profile similar to other drug in its class, it may actually be more potent, which could contribute to its value for patients with relapsed or refractory disease in particular.”
Of those with relapsed/refractory disease, 93% had a baseline ECOG score ≤1. In addition, 75% had undergone three or more prior systemic therapies, and 61% were less than 6 months from their most recent therapy. More than 50% had either 17p deletion or TP53 mutation.
“There was an overwhelming response,” Flinn said. “Ninety-eight percent of patients had a reduction in adenopathy and 89% of these patients treated with the 25 mg dose had a reduction of lymph nodes of more than 50%.”
The best overall response in evaluable patients to date was 47%, according to Flinn. The ORR for the 27 evaluable patients treated at doses ≤25 mg was 48%.
Pharmacokinetics, pharmacodynamics and clinical activity data indicated twice-daily 25 mg IPI-145 is a biologically active dose in relapsed, refractory CLL. This dose has, therefore, been chosen for an upcoming randomized phase 3 trial in relapsed, refractory CLL.
In a subset of patients assigned to a dose-escalation phase, researchers found that twice-daily 75 mg IPI-145 was the maximum tolerated dose.
The most common grade ≥3 adverse events were transient neutropenia (n=9), anemia (n=4), febrile neutropenia (n=3) and pneumonitis (n=3).
For more information:
Flinn I. Abstract #677. Presented at: ASH Annual Meeting and Exhibition; Dec. 7-10, 2013; New Orleans.
Disclosure: The researchers report research funding from Allos, Celgene, Infinity Pharmaceuticals, Kyowa, Lilly, Medivation, Millennium and Seattle Genetics.