On May 26, 2015 Infinity Pharmaceuticals reported new preclinical data for duvelisib (IPI-145), an investigational, oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma (Press release, Infinity Pharmaceuticals, MAY 26, 2015, View Source [SID:1234504829]). Schedule your 30 min Free 1stOncology Demo! In vitro studies demonstrated synergy with standard-of-care therapies and emerging agents in development for hematologic malignancies, including duvelisib in combination with venetoclax, in combination with ibrutinib and in combination with dexamethasone. Additionally, in preclinical studies with each of these three combinations, significant inhibition of lymphoma tumor growth was observed compared to each of these agents alone. These data will be presented at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago, Ill. on Sunday, May 31, 2015.
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"Targeted combinations have the potential to further improve treatment options for patients, and Infinity’s translational research team continues to collaborate with AbbVie, our global partner for duvelisib in oncology, to identify therapies that may be synergistic with duvelisib," stated Vito Palombella, Infinity’s chief scientific officer. "This research supports further development of duvelisib in combination with approved and investigational medicines, including venetoclax."
"Additionally, preclinical research evaluating the activity of PI3K-delta isoform selective inhibitors and PI3K-gamma isoform selective inhibitors together shows that inhibiting both isoforms leads to greater tumor growth inhibition than either isoform alone, suggesting dual inhibition of PI3K-delta and PI3K-gamma has complementary effects on malignant B-cell growth and survival in these preclinical models," Dr. Palombella continued.
Preclinical and Translational Combination Data for Duvelisib (Abstract #8559)
New preclinical and translational research conducted in collaboration with researchers at AbbVie will be reported at ASCO (Free ASCO Whitepaper) 2015 on Sunday, May 31, from 8:00 a.m. – 11:30 a.m. CDT (9:00 a.m. – 12:30 p.m. EDT) in a poster presentation, "High throughput in vitro combination sensitivity screen in hematologic malignancies with the phosphoinositide-3-kinase (PI3K)-delta,gamma inhibitor, duvelisib."
As part of Infinity and AbbVie’s ongoing joint efforts to identify compounds synergistic with duvelisib, researchers conducted an in vitro high-throughput combination screen using a panel of cell lines and various drug combinations. In vitro synergy was observed with standard-of-care therapies and emerging agents in development for hematologic malignancies, including duvelisib in combination with venetoclax, in combination with ibrutinib and in combination with dexamethasone.
Additionally, in preclinical human xenograft studies with each of these three combinations, significant inhibition of lymphoma tumor growth was observed compared to each of these agents alone. These data support the use of duvelisib as part of combination therapy and provide additional rationale for the first clinical study of duvelisib in combination with venetoclax.
Researchers also evaluated the impact of dual inhibition of PI3K-delta and PI3K-gamma using isoform-selective inhibitors in preclinical models. Combined inhibition of PI3K-delta and PI3K-gamma led to greater tumor growth inhibition compared to the inhibition of either PI3K isoform alone, suggesting that dual inhibition of PI3K-delta and PI3K-gamma with duvelisib has complementary effects on malignant B-cell growth and survival in these preclinical models.
Additional Duvelisib Presentations at ASCO (Free ASCO Whitepaper) 2015
In total, four duvelisib presentations will take place on Sunday, May 31, 2015, during a poster session from 8:00 a.m. to 11:30 a.m. CDT in South Hall A at McCormick Place. In addition to the preclinical data reported today, duvelisib presentations at ASCO (Free ASCO Whitepaper) 2015 will include the following:
Phase 1 data describing the clinical activity and pharmacodynamics effects of duvelisib in a cohort of treatment-naïve patients with chronic lymphocytic leukemia (CLL) (Abstract #7074)
Translational data providing insight into the mechanism by which duvelisib disrupts communication between tumor cells and the supporting microenvironment in CLL (Abstract #7072)
A "trials in progress" poster highlighting SYNCHRONY, a Phase 1b study of duvelisib and obinutuzumab in CLL patients whose disease is refractory to or has relapsed while receiving a BTK inhibitor (Abstract #TPS7100)
About Duvelisib
Duvelisib is a dual, oral inhibitor of phosophoinositide-3-kinase (PI3K)-delta and PI3K-gamma that is being jointly developed by Infinity Pharmaceuticals, Inc. and AbbVie Inc. The PI3K pathway is known to play a critical role in regulating the growth and survival of certain types of blood cancers. Duvelisib is designed to block the growth and survival of tumor cells by inhibiting PI3K-delta and PI3K-gamma signaling. The investigational agent is being evaluated in registration-focused studies, including DYNAMOTM, a Phase 2 study in patients with refractory indolent non-Hodgkin lymphoma, DYNAMO+R, a Phase 3 study in patients with previously treated follicular lymphoma, and DUOTM, a Phase 3 study in patients with relapsed/refractory chronic lymphocytic leukemia. Duvelisib is an investigational compound and its safety and efficacy have not been evaluated by the U.S. Food and Drug Administration or any other health authority.