On September 6, 2017 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to improve the survival and quality of life of cancer patients, reported positive top-line results from the Phase 3 DUO study evaluating the efficacy and safety of duvelisib, a first in class oral dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (Press release, Verastem, SEP 6, 2017, View Source [SID1234520395]).
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Regarding the DUO study’s primary endpoint of progression free survival (PFS) as determined by Independent Review Committee (IRC), oral duvelisib monotherapy showed superiority over ofatumumab, an approved standard of care treatment for patients with CLL/SLL, achieving a statistically significant improvement in median PFS of 13.3 months, compared to 9.9 months for ofatumumab with a hazard ratio (HR) of 0.52 (p<0.0001), representing a 48% reduction in the risk of progression or death. Median PFS in the subset of patients with 17p deletion randomized to duvelisib was also significantly higher (12.7 months compared to 9.0 months for ofatumumab; HR of 0.41, p=0.0011).
"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," commented Ian Flinn, MD, PhD, Director of the Blood Cancer Research Program at Sarah Cannon Research Institute and the Lead Investigator on the DUO study. "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. For our patients with CLL/SLL, 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."
Verastem plans to share these clinical data with the U.S. Food and Drug Administration (FDA) with the goal of filing a New Drug Application (NDA) with the FDA during the first half of 2018. The duvelisib NDA submission will be supported by favorable results from both the DUO study in CLL/SLL and the DYNAMO study in indolent non-Hodgkin’s lymphoma (iNHL), which also achieved its primary endpoint with an ORR of 46% (p<0.0001).
In the Phase 3 DUO study, 319 patients were randomized 1:1 to receive either duvelisib 25mg twice daily until disease progression or unacceptable toxicity or ofatumumab, an approved standard of care treatment for use in CLL/SLL, per its label with an initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2,000 mg. In addition to the primary endpoint of PFS in the ITT population a stratification factor to evaluate the outcome in the patients with 17p deletion CLL/SLL, a known poor prognostic subgroup, was conducted. PFS and other efficacy endpoints were analyzed using response determinations per the IRC using modified iwCLL/IWG criteria.
Duvelisib monotherapy had a manageable safety profile, with results from this study consistent with the well-characterized safety profile of duvelisib monotherapy in patients with advanced hematologic malignancies. Verastem intends to submit detailed results from the Phase 3 DUO study for publication in a peer-reviewed medical journal and for presentation at an upcoming scientific meeting.
"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," said Robert Forrester, President and Chief Executive Officer of Verastem. "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."
About Duvelisib
Duvelisib is an investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib is currently being evaluated in late- and mid-stage clinical trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed or refractory CLL/SLL,4 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory iNHL.5 Both DUO and DYNAMO achieved their primary endpoints upon topline analysis of efficacy data. Duvelisib is also being evaluated for the treatment of other hematologic malignancies, including T-cell lymphoma, through investigator-sponsored studies.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.