Preclinical studies showed that treatment with IPI-145 suppressed PI3K signaling and cell growth in a subset of DLBCL cell lines. In several of these cells lines, treatment with IPI-145 and ibrutinib (a Bruton's tyrosine kinase, or BTK, inhibitor) led to a synergistic suppression of cell growth, providing a potential rationale for exploring IPI-145 in combination with ibrutinib in DLBCL.
Preclinical Data in T-ALL
In the presentation “The potent PI3K-delta,gamma inhibitor, IPI-145, exhibits preclinical activity in murine and human T-cell acute lymphoblastic leukemia” (Abstract #1438), data from preclinical studies of IPI-145 tested in both human and rodent cell lines of T-ALL showed that treatment with IPI-145 inhibited the growth of a subset of T-ALL cells deficient for PTEN (a phosphatase and tumor suppressor gene). Treatment with IPI-145 led to a greater inhibition of T-ALL cell growth compared to treatment with molecules selective for only PI3K-delta or PI3K-gamma, providing a potential rationale for combined PI3K-delta and -gamma inhibition for the treatment of T-ALL.
In a separate press release issued today, Infinity reported updated Phase 1 data in patients with indolent non-Hodgkin lymphoma (iNHL) which showed that IPI-145 was clinically active, with an overall response rate of 73 percent (11 of 15 evaluable patients) and a 20 percent complete response rate (3 of 15 patients). Eight patients (53 percent) remain progression-free for over one year. Additionally, translational data showed that IPI-145 affects key signaling molecules in the tumor microenvironment, providing a potential mechanistic rationale for the clinical activity of IPI-145 observed in patients with iNHL and chronic lymphocytic leukemia (CLL).
The posters presented at the 55th Annual Meeting of ASH are available in the Publications Archive on Infinity’s website
About the Development of IPI-145 for the Treatment of Blood Cancers
Infinity is developing IPI-145, an oral inhibitor of Class I PI3K-delta,gamma. The PI3Ks are a family of enzymes involved in multiple cellular functions, including cell proliferation and survival, cell differentiation, cell migration and immunity. The PI3K-delta,gamma isoforms are preferentially expressed in leukocytes (white blood cells), where they have distinct and mostly non-overlapping roles in immune cell development and function. Targeting PI3K-delta and PI3K-gamma may provide multiple opportunities to develop differentiated therapies for the treatment of hematologic malignancies as well as inflammatory diseases.