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Duvelisib extends PFS in chronic lymphocytic leukemia, small lymphocytic lymphoma
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A phase 3 study designed to evaluate duvelisib for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma achieved its primary endpoint of superior PFS compared with standard therapy.
Duvelisib (Verastem) is a first-in-class oral dual inhibitor of phosphoinositide 3-kinase-delta and phosphoinositide 3-kinase-gamma enzymes.
The phase 3 DUO study evaluated the efficacy and safety of duvelisib compared with ofatumumab (Arzerra, Novartis) in 319 patients with CLL or small lymphocytic lymphoma.
Researchers randomly assigned half of the patients to receive 25 mg duvelisib twice daily until disease progression or unacceptable toxicity. The other half received an initial infusion of 300 mg ofatumumab, followed by seven weekly infusions and four monthly infusions of 2,000 mg.
PFS in the intent-to-treat population as determined by an independent review committee served as the primary endpoint. Researchers also evaluated a stratification factor to determine outcomes in patients with 17p deletion.
Patients treated with duvelisib achieved superior median PFS, demonstrating a 48% reduction in the risk for progression or death compared with ofatumumab-treated patients arm (median PFS, 13.3 months vs. 9.9 months; HR = 0.52; P <.0001).
Among the subgroup of patients with 17p deletion, those treated with duvelisib achieved median PFS (12.7 months vs. 9 months; HR = 0.41; P = .001).
Duvelisib’s safety profile appeared consistent with that observed in prior studies.
“Although the treatment of CLL/small lymphocytic lymphoma has advanced in recent years, there remains a substantial unmet need with many patients progressing or relapsing following the available therapies,” lead investigator Ian Flinn, MD, PhD, director of the Blood Cancer Research Program at Sarah Cannon Research Institute, said in a Verastem-issued press release.
“These positive results from the randomized DUO study demonstrate that duvelisib prolongs PFS with a manageable safety profile in patients with relapsed or refractory CLL/SLL, including in high-risk patients with the 17p deletion,” Flinn added. “For our patients with CLL/small lymphocytic lymphoma, and for the physicians who treat them, a convenient, oral monotherapy that is taken at home would be a valuable addition to the treatment landscape.”
In addition, the DYNAMO trial — designed to evaluate duvelisib in patients with indolent non-Hodgkin’s lymphoma — also achieved its primary endpoint, with an ORR of 46% (P < .0001).
Verastem intends to file a new drug application — including data from the DUO trial and DYANMO study – with the FDA next year, according to the press release.
“We are extremely grateful to the patients, caregivers and investigators who participated in the DUO study and we are pleased to be that much closer to delivering on our mission to develop drugs that improve the lives of patients with cancer,” Robert Forrester, president and CEO of Verastem, said in the release. “Duvelisib was an important strategic acquisition for Verastem. Both of our late-stage trials with duvelisib monotherapy (DUO and DYNAMO) have now achieved their primary endpoints, highlighting the significant potential of duvelisib in the treatment of advanced hematologic malignancies. We anticipate sharing these results with the FDA in preparation for a potential NDA filing during the first half of 2018 and look forward to exploring subsequent development opportunities for duvelisib in additional cancers.”