–Clinical Activity Observed in High-Risk CLL Patients–
– New Translational Data Provide Further Insight Into the Role of PI3K-Delta and PI3K-Gamma Inhibition in Hematologic Malignancies –
CAMBRIDGE, MA, USA I May 31, 2015 I Infinity Pharmaceuticals, Inc. (NASDAQ:INFI) today announced new clinical data for duvelisib (IPI-145), an oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma in patients with treatment-naïve chronic lymphocytic leukemia (CLL), a potentially fatal hematologic malignancy (blood cancer). Data from the Phase 1 study showed that duvelisib was highly active in this patient population cohort, with an overall response rate of 88 percent as defined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria, including 15 partial responses among 17 efficacy evaluable patients. These data will be presented at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill. on Sunday, May 31, 2015.
“It is encouraging to see such a high monotherapy response rate reported in treatment-naïve patients with chronic lymphocytic leukemia, the majority of whom in this study were identified as high-risk and with a less favorable prognosis,” commented Manish R. Patel, MD, Florida Cancer Specialists/Sarah Cannon Research Institute and an investigator for the trial. “These data support further evaluating duvelisib as a front-line treatment option for patients with CLL, including novel combinations with other emerging targeted treatments.”
Today Infinity also announced new translational data demonstrating that treatment with duvelisib resulted in a decrease in key mediators known to be involved in the communication between CLL cells and the tumor microenvironment. These data further support the investigation of dual inhibition of PI3K-delta and PI3K-gamma with duvelisib as a therapeutic strategy for the treatment of CLL.
Clinical Data for Duvelisib in Treatment-Naïve CLL Patients (Abstract #7074)
New clinical data from the Phase 1 study of duvelisib will be reported at ASCO 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, “Early clinical activity and pharmacodynamic effects of duvelisib, a PI3K-δ,γ inhibitor, in patients with treatment-naïve CLL.” The study included 18 treatment-naïve CLL patients, with 17 evaluable for response who received duvelisib dosed at 25 mg dose twice daily (BID), which is the dose being administered in ongoing registration studies. All patients in this study were age 65 or over or high-risk, defined as having 17p deletions or p53 mutations. Patients with CLL with 17p deletions or p53 mutations generally have a poor response to chemotherapy and worse prognosis.1
Data showed that duvelisib is clinically active in patients with treatment-naïve CLL, with an 88 percent overall response rate (15 partial responses out of 17 evaluable patients) as defined by the iwCLL criteria. Additionally, two patients exhibited stable disease. The median time to response was 3.7 months. The median progression free survival (PFS) and median overall survival (OS) have not yet been reached, with a 92 percent PFS rate and 94 percent OS rate at 18 months.
The majority of adverse events were grade 1 or grade 2 and clinically manageable. The most common grade 3 side effects among the 18 enrolled patients were diarrhea (22 percent, 4 patients), increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (17 percent, 3 patients), and rash (11 percent, 2 patients). Twenty-eight percent (5 patients) had grade 4 neutropenia or decreases in neutrophil count. There were no grade 4 events of diarrhea, increases in ALT/AST or rash. Six patients discontinued treatment due to an adverse event.
Research also showed that duvelisib treatment inhibited the PI3K pathway and CLL cell proliferation in treatment-naïve CLL patients, and also reduced serum levels of chemokines and cytokines produced by both CLL cells and the tumor microenvironment. Taken together, these Phase 1 clinical and translational data support further development of duvelisib in treatment-naïve CLL, including combination studies with other targeted therapies.
New Translational CLL Data from the Phase 1 Study of Duvelisib (Abstract #7072)
New translational data will be reported at ASCO 2015 on Sunday, May 31, from 8:00 a.m. – 11:30 a.m. CDT in a poster presentation, “Serum chemokines and cytokines in CLL patients treated with duvelisib, a PI3K-delta,gamma inhibitor.”
Data from translational studies demonstrated that in patients with relapsed/refractory CLL, treatment with duvelisib resulted in a decrease in key chemokines and cytokines known to be involved in the communication between CLL cells and the tumor microenvironment, including stromal cells, T-cells and myeloid cells. This research provides further insight into the mechanism by which duvelisib disrupts communication between the tumor cells and the supporting microenvironment in CLL and supports the development of duvelisib for the treatment of CLL.
Additional Duvelisib Presentations at ASCO 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 clinical and translational data reported today, duvelisib presentations at ASCO 2015 will include the following:
- Preclinical data for duvelisib demonstrating synergy with standards-of-care and emerging targeted therapeutics in development for hematologic malignancies, including duvelisib in combination with venetoclax (Abstract #8559)
- A “trials in progress” poster highlighting SYNCHRONY, a Phase 1b study of duvelisib in CLL patients whose disease is refractory to or has relapsed while receiving a BTK inhibitor (Abstract # TPS7100)
About Duvelisib
Duvelisib is an investigational, oral, dual inhibitor of phosophoinositide-3-kinase (PI3K)-delta and PI3K-gamma that is being jointly developed by Infinity Pharmaceuticals, Inc. and AbbVie Inc. in oncology. 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.
Duvelisib 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 also being evaluated in CONTEMPO, a Phase 1b/2 study in treatment-naïve patients with follicular lymphoma and SYNCHRONY, a Phase 1b study in CLL patients whose disease is refractory to or has relapsed while receiving a BTK inhibitor.
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.
About Infinity Pharmaceuticals, Inc.
Infinity is an innovative biopharmaceutical company dedicated to discovering, developing and delivering best-in-class medicines to people with difficult-to-treat diseases. Infinity combines proven scientific expertise with a passion for developing novel small molecule drugs that target emerging disease pathways. For more information on Infinity, please refer to the company’s website at www.infi.com.
SOURCE: Infinity Pharmaceuticals
Post Views: 63
–Clinical Activity Observed in High-Risk CLL Patients–
– New Translational Data Provide Further Insight Into the Role of PI3K-Delta and PI3K-Gamma Inhibition in Hematologic Malignancies –
CAMBRIDGE, MA, USA I May 31, 2015 I Infinity Pharmaceuticals, Inc. (NASDAQ:INFI) today announced new clinical data for duvelisib (IPI-145), an oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma in patients with treatment-naïve chronic lymphocytic leukemia (CLL), a potentially fatal hematologic malignancy (blood cancer). Data from the Phase 1 study showed that duvelisib was highly active in this patient population cohort, with an overall response rate of 88 percent as defined by the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria, including 15 partial responses among 17 efficacy evaluable patients. These data will be presented at the 2015 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Ill. on Sunday, May 31, 2015.
“It is encouraging to see such a high monotherapy response rate reported in treatment-naïve patients with chronic lymphocytic leukemia, the majority of whom in this study were identified as high-risk and with a less favorable prognosis,” commented Manish R. Patel, MD, Florida Cancer Specialists/Sarah Cannon Research Institute and an investigator for the trial. “These data support further evaluating duvelisib as a front-line treatment option for patients with CLL, including novel combinations with other emerging targeted treatments.”
Today Infinity also announced new translational data demonstrating that treatment with duvelisib resulted in a decrease in key mediators known to be involved in the communication between CLL cells and the tumor microenvironment. These data further support the investigation of dual inhibition of PI3K-delta and PI3K-gamma with duvelisib as a therapeutic strategy for the treatment of CLL.
Clinical Data for Duvelisib in Treatment-Naïve CLL Patients (Abstract #7074)
New clinical data from the Phase 1 study of duvelisib will be reported at ASCO 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, “Early clinical activity and pharmacodynamic effects of duvelisib, a PI3K-δ,γ inhibitor, in patients with treatment-naïve CLL.” The study included 18 treatment-naïve CLL patients, with 17 evaluable for response who received duvelisib dosed at 25 mg dose twice daily (BID), which is the dose being administered in ongoing registration studies. All patients in this study were age 65 or over or high-risk, defined as having 17p deletions or p53 mutations. Patients with CLL with 17p deletions or p53 mutations generally have a poor response to chemotherapy and worse prognosis.1
Data showed that duvelisib is clinically active in patients with treatment-naïve CLL, with an 88 percent overall response rate (15 partial responses out of 17 evaluable patients) as defined by the iwCLL criteria. Additionally, two patients exhibited stable disease. The median time to response was 3.7 months. The median progression free survival (PFS) and median overall survival (OS) have not yet been reached, with a 92 percent PFS rate and 94 percent OS rate at 18 months.
The majority of adverse events were grade 1 or grade 2 and clinically manageable. The most common grade 3 side effects among the 18 enrolled patients were diarrhea (22 percent, 4 patients), increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (17 percent, 3 patients), and rash (11 percent, 2 patients). Twenty-eight percent (5 patients) had grade 4 neutropenia or decreases in neutrophil count. There were no grade 4 events of diarrhea, increases in ALT/AST or rash. Six patients discontinued treatment due to an adverse event.
Research also showed that duvelisib treatment inhibited the PI3K pathway and CLL cell proliferation in treatment-naïve CLL patients, and also reduced serum levels of chemokines and cytokines produced by both CLL cells and the tumor microenvironment. Taken together, these Phase 1 clinical and translational data support further development of duvelisib in treatment-naïve CLL, including combination studies with other targeted therapies.
New Translational CLL Data from the Phase 1 Study of Duvelisib (Abstract #7072)
New translational data will be reported at ASCO 2015 on Sunday, May 31, from 8:00 a.m. – 11:30 a.m. CDT in a poster presentation, “Serum chemokines and cytokines in CLL patients treated with duvelisib, a PI3K-delta,gamma inhibitor.”
Data from translational studies demonstrated that in patients with relapsed/refractory CLL, treatment with duvelisib resulted in a decrease in key chemokines and cytokines known to be involved in the communication between CLL cells and the tumor microenvironment, including stromal cells, T-cells and myeloid cells. This research provides further insight into the mechanism by which duvelisib disrupts communication between the tumor cells and the supporting microenvironment in CLL and supports the development of duvelisib for the treatment of CLL.
Additional Duvelisib Presentations at ASCO 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 clinical and translational data reported today, duvelisib presentations at ASCO 2015 will include the following:
- Preclinical data for duvelisib demonstrating synergy with standards-of-care and emerging targeted therapeutics in development for hematologic malignancies, including duvelisib in combination with venetoclax (Abstract #8559)
- A “trials in progress” poster highlighting SYNCHRONY, a Phase 1b study of duvelisib in CLL patients whose disease is refractory to or has relapsed while receiving a BTK inhibitor (Abstract # TPS7100)
About Duvelisib
Duvelisib is an investigational, oral, dual inhibitor of phosophoinositide-3-kinase (PI3K)-delta and PI3K-gamma that is being jointly developed by Infinity Pharmaceuticals, Inc. and AbbVie Inc. in oncology. 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.
Duvelisib 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 also being evaluated in CONTEMPO, a Phase 1b/2 study in treatment-naïve patients with follicular lymphoma and SYNCHRONY, a Phase 1b study in CLL patients whose disease is refractory to or has relapsed while receiving a BTK inhibitor.
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.
About Infinity Pharmaceuticals, Inc.
Infinity is an innovative biopharmaceutical company dedicated to discovering, developing and delivering best-in-class medicines to people with difficult-to-treat diseases. Infinity combines proven scientific expertise with a passion for developing novel small molecule drugs that target emerging disease pathways. For more information on Infinity, please refer to the company’s website at www.infi.com.
SOURCE: Infinity Pharmaceuticals
Post Views: 63
