Date: 2014-12-11
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, being held December 6-9 in San Francisco, CA
Company: Infinity Pharmaceuticals (USA - MA)
Product: duvelisib (IPI-145)
Action
mechanism: phosphoinositide 3-kinase (PI3K) inhibitor. Duvelisib is 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. Infinity and AbbVie Inc. are developing duvelisib, 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 Class 1 PI3K-delta and PI3K-gamma isoforms are preferentially expressed in leukocytes, or white blood cells, where they have distinct and predominantly non-overlapping roles in key cellular functions, including cell proliferation, cell differentiation, cell migration and activation. Targeting PI3K-delta and PI3K-gamma may provide multiple opportunities to develop differentiated therapies for the treatment of hematologic malignancies. In 2013, Infinity launched the DUETTS™ (Duvelisib Trials in Hematologic Malignancies) program, a worldwide investigation of duvelisib in blood cancers. As part of the DUETTS program, patient enrollment is ongoing in DYNAMO™, a Phase 2 monotherapy study designed to evaluate the safety and efficacy of duvelisib in patients with refractory indolent non-Hodgkin lymphoma (iNHL) (NCT01882803), and DUO™, a Phase 3 monotherapy study designed to evaluate the safety and efficacy of duvelisib in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) (NCT02004522). DYNAMO+RTM, a Phase 3 study of duvelisib in combination with rituximab in patients with previously treated follicular lymphoma (NCT02204982), is expected to start in 2014. Additionally, a Phase 1 study of duvelisib in patients with advanced blood cancers is ongoing (NCT01476657).
Disease: relapsed/refractory indolent non-Hodgkin lymphoma (iNHL)
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On December 9, 2014, Infinity Pharmaceuticals reported updated data from a Phase 1 monotherapy study of duvelisib (IPI-145), an inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, which showed activity among patients with relapsed/refractory indolent non-Hodgkin lymphoma (iNHL). In the study, duvelisib demonstrated an overall response rate of 72 percent, including a 33 percent complete response rate, among 18 patients with iNHL who received the dose administered in ongoing registration-focused studies. In a separate presentation, updated Phase 1 data were also reported showing the activity of duvelisib in patients with relapsed/refractory T-cell lymphoma. These data were presented at the 56th Annual Meeting of the American Society of Hematology (ASH). Phase 1 Study Shows Activity in Patients with iNHL (Abstract #802): Updated Phase 1 data in patients with relapsed/refractory iNHL were reported in an oral presentation, \"A Phase 1 evaluation of duvelisib (IPI-145), a PI3K-delta,gamma inhibitor, in patients with relapsed/refractory iNHL.\" The study included 34 patients evaluable for response, of which 18 received duvelisib dosed at 25 mg twice daily (BID), which is the dose being administered in ongoing registration-focused studies, DYNAMOTM and DYNAMO+R. Data showed that duvelisib administered at 25 mg BID was clinically active, with a 72 percent overall response rate (13 of 18 evaluable patients) and a 33 percent complete response rate (6 of 18 evaluable patients). Among patients with follicular lymphoma, the overall response rate was 69 percent (9 of 13 evaluable patients), including a 38 percent complete response rate (5 of 13 evaluable patients). The median progression free survival and median overall survival have not yet been reached, with 69 percent progression-free and 89 percent overall survival at 24 months. At the 25 mg BID dose, the most common Grade 3 side effects were increases in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (32 percent), diarrhea (16 percent), neutropenia and pneumonia (11 percent each). Grade 4 neutropenia was 11 percent (2 patients), Grade 4 ALT or AST increase was 5 percent (1 patient) and Grade 4 pneumonia was 5 percent (1 patient). There were no Grade 4 events of diarrhea. Phase 1 Trial Results Show Response in T-Cell Lymphoma (Abstract #803): Infinity also reported Phase 1 data showing the activity of duvelisib in patients with T-cell lymphoma, which accounts for approximately 15 percent of all non-Hodgkin lymphomas in the U.S.
Treatment with duvelisib in heavily pre-treated patients with relapsed/refractory T-cell lymphoma led to an overall response rate of 42 percent (14 of 33 patients evaluable for response), including 2 complete responses and 12 partial responses. Among the 15 patients with peripheral T-cell lymphoma (PTCL) who were evaluable for response, duvelisib led to 2 complete responses and 6 partial responses, for an overall response rate of 53 percent. Among the 18 patients with cutaneous T-cell lymphoma (CTCL) evaluable for response, duvelisib led to 6 partial responses, for an overall response rate of 33 percent. Stable disease was observed in 1 patient with PTCL and 6 patients with CTCL.
The Grade 3 side effects in patients with T-cell lymphoma included increases in ALT or AST (31 percent, 11 patients), rash (17 percent, 6 patients) and pneumonia (14 percent, 5 patients). Two patients (6 percent) had Grade 4 ALT or AST increases and 1 patient (3 percent) had Grade 4 pneumonia. The majority of patients (27 of 35) received duvelisib dosed at 75 mg BID.
These data were reported in an oral presentation, \"Duvelisib (IPI-145), a phosphoinositide-3-kinase-delta,gamma inhibitor, shows activity in patients with relapsed/refractory T-cell lymphoma.\"
