Duvelisib, a first-in-class dual inhibitor of PI3K-delta and PI3K-gamma, improved the median progression-free survival of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) by about 3.5 months compared with the current standard, ofatumumab, according to results of the DUO study announced by Verastem, the manufacturer of duvelisib.
“Although the treatment of CLL/SLL has advanced in recent years, there remains a substantial unmet need with many patients progressing or relapsing following the available therapies,” said DUO study lead investigator Ian Flinn, MD, PhD, of the Sarah Cannon Research Institute in Nashville, Tennessee, in a press release. “These positive results from the randomized DUO study demonstrate that duvelisib prolongs progression-free survival (PFS) with a manageable safety profile in patients with relapsed or refractory CLL/SLL, including in high-risk patients with the 17p deletion.”
The phase III DUO study included 319 patients with CLL/SLL who were randomly assigned to either duvelisib 25 mg twice daily or ofatumumab. The primary endpoint of the study was PFS.
An independent review committee measured median PFS of duvelisib as 13.3 months compared with 9.9 months for ofatumumab, with a 48% reduction in the risk of progression or death (hazard ratio [HR], 0.52; P < .0001).
The researchers also looked at outcomes in CLL/SLL patients with a 17p deletion, a known poor prognostic subgroup. Among these patients, duvelisib also significantly prolonged PFS (12.7 months vs 9 months; HR, 0.41; P = .0011).
Safety results from this study were consistent with those of prior monotherapy studies of the drug.
“We remain on track to submit a New Drug Application to the US Food and Drug Administration during the first quarter of 2018 requesting full approval of duvelisib for the treatment of patients with relapsed or refractory CLL/SLL,” said Diep Le, MD, PhD, chief medical officer of Verastem, in a press release.