Thirty-Eight Percent Response Rate in Patients with T-Cell Lymphomas, Suggesting Broad Potential of IPI-145 in Blood Cancers
CAMBRIDGE, MA, USA I January 24, 2014 I Infinity Pharmaceuticals, Inc. (INFI) reported encouraging data from its ongoing Phase 1 study of IPI-145, its oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, in patients with relapsed/refractory T-cell lymphoma, a difficult-to-treat hematologic malignancy (blood cancer) with few available treatment options. Preliminary data showed that IPI-145 is clinically active in patients with T-cell lymphoma, with an overall response rate of 38 percent, including one complete response and nine partial responses among 26 patients evaluable for response. These findings were reported during the 6th Annual T-Cell Lymphoma Forum being held from January 23 – 25, 2014, in San Francisco, CA.
“The clinical data for IPI-145 in patients with T-cell lymphoma underscore the potential of IPI-145 to treat a broad range of blood cancers,” stated Julian Adams, Ph.D., president of R&D at Infinity. “IPI-145 has already shown clinical activity in indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia, and Infinity is advancing IPI-145 into late-stage development in these two hematologic malignancies. These data in patients with T-cell lymphoma help further our understanding of the clinical potential of IPI-145 in additional indications and may help to guide our future development plans.”
Summary of Phase 1 Data of IPI-145 in T-Cell Lymphoma
The poster presentation, “Clinical activity of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with relapsed/refractory T-cell lymphoma: Preliminary results from an ongoing Phase 1 study,” included 30 patients in the safety population, of which 26 were evaluable for clinical activity. Patients enrolled in the study had advanced disease, with a median of five prior systemic therapies (range: 1 – 11) and a median of one month from last therapy to first dose on study (range: 0.2 – 12).
Clinical Activity
Treatment with IPI-145 in patients with T-cell lymphomas led to an overall response rate of 38 percent, including one complete response and nine partial responses among 26 patients evaluable for response. Among the 11 patients with peripheral T-cell lymphoma (PTCL) evaluable for activity, IPI-145 led to one complete response and five partial responses, for an overall response rate (ORR) of 55 percent. Among the 15 patients with cutaneous T-cell lymphoma (CTCL) evaluable for activity, IPI-145 led to four partial responses, for an ORR of 27 percent. Stable disease was observed in seven patients with CTCL. The onset of activity was rapid, with a median time to response of 1.9 months (range: 1.5 – 2.7) for patients with PTCL and 2.4 months (range: 1.7 – 3.8) for patients with CTCL. The median number of treatment cycles for the 13 patients with PTCL was 2.2 (range: 0.5 – 8), and the median number of treatment cycles for the 17 patients with CTCL was 3.1 (range: 0.4 – 11). Four patients with PTCL and three patients with CTCL remain on treatment.
Safety and Pharmacodynamics
IPI-145 was generally well tolerated, with the majority of patients (20 of 30) receiving IPI-145 dosed at 75 mg twice daily (BID). The most common Grade 3 side effects were increases in ALT or AST (two liver enzymes) (10 patients; 33 percent), rash (4 patients; 13 percent) and fatigue (3 patients; 10 percent). One patient (3 percent) had Grade 4 ALT or AST increases.
Data also showed that treatment with IPI-145 led to decreases in serum levels of cytokines and chemokines known to play important roles in lymphocyte trafficking and function, further supporting the rationale that inhibiting PI3K-delta and PI3K-gamma has the potential to provide a therapeutic benefit for T-cell lymphoma as well as other blood cancers.
The poster is available in the Publications Archive on Infinity’s website http://www.infi.com/product-candidates-publications.asp.
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.
Infinity has launched DUETTSTM, a worldwide investigation of IPI-145 in blood cancers. As part of the DUETTS program, Infinity is currently enrolling patients in DYNAMOTM, a Phase 2 monotherapy study designed to evaluate the safety and efficacy of IPI-145 in patients with refractory indolent non-Hodgkin lymphoma (iNHL) (ClinicalTrials.gov Identifier NCT01882803), and DUOTM, a Phase 3 monotherapy study designed to evaluate the safety and efficacy of IPI-145 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) (NCT02004522).
An investigator-sponsored Phase 1b, open-label study of IPI-145 in patients with B-cell NHL, CLL and T-cell lymphoma in combination with rituximab (a monoclonal antibody therapy), bendamustine (a chemotherapy) or both rituximab and bendamustine is also open for enrollment (NCT01871675).
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: 99
Thirty-Eight Percent Response Rate in Patients with T-Cell Lymphomas, Suggesting Broad Potential of IPI-145 in Blood Cancers
CAMBRIDGE, MA, USA I January 24, 2014 I Infinity Pharmaceuticals, Inc. (INFI) reported encouraging data from its ongoing Phase 1 study of IPI-145, its oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, in patients with relapsed/refractory T-cell lymphoma, a difficult-to-treat hematologic malignancy (blood cancer) with few available treatment options. Preliminary data showed that IPI-145 is clinically active in patients with T-cell lymphoma, with an overall response rate of 38 percent, including one complete response and nine partial responses among 26 patients evaluable for response. These findings were reported during the 6th Annual T-Cell Lymphoma Forum being held from January 23 – 25, 2014, in San Francisco, CA.
“The clinical data for IPI-145 in patients with T-cell lymphoma underscore the potential of IPI-145 to treat a broad range of blood cancers,” stated Julian Adams, Ph.D., president of R&D at Infinity. “IPI-145 has already shown clinical activity in indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia, and Infinity is advancing IPI-145 into late-stage development in these two hematologic malignancies. These data in patients with T-cell lymphoma help further our understanding of the clinical potential of IPI-145 in additional indications and may help to guide our future development plans.”
Summary of Phase 1 Data of IPI-145 in T-Cell Lymphoma
The poster presentation, “Clinical activity of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with relapsed/refractory T-cell lymphoma: Preliminary results from an ongoing Phase 1 study,” included 30 patients in the safety population, of which 26 were evaluable for clinical activity. Patients enrolled in the study had advanced disease, with a median of five prior systemic therapies (range: 1 – 11) and a median of one month from last therapy to first dose on study (range: 0.2 – 12).
Clinical Activity
Treatment with IPI-145 in patients with T-cell lymphomas led to an overall response rate of 38 percent, including one complete response and nine partial responses among 26 patients evaluable for response. Among the 11 patients with peripheral T-cell lymphoma (PTCL) evaluable for activity, IPI-145 led to one complete response and five partial responses, for an overall response rate (ORR) of 55 percent. Among the 15 patients with cutaneous T-cell lymphoma (CTCL) evaluable for activity, IPI-145 led to four partial responses, for an ORR of 27 percent. Stable disease was observed in seven patients with CTCL. The onset of activity was rapid, with a median time to response of 1.9 months (range: 1.5 – 2.7) for patients with PTCL and 2.4 months (range: 1.7 – 3.8) for patients with CTCL. The median number of treatment cycles for the 13 patients with PTCL was 2.2 (range: 0.5 – 8), and the median number of treatment cycles for the 17 patients with CTCL was 3.1 (range: 0.4 – 11). Four patients with PTCL and three patients with CTCL remain on treatment.
Safety and Pharmacodynamics
IPI-145 was generally well tolerated, with the majority of patients (20 of 30) receiving IPI-145 dosed at 75 mg twice daily (BID). The most common Grade 3 side effects were increases in ALT or AST (two liver enzymes) (10 patients; 33 percent), rash (4 patients; 13 percent) and fatigue (3 patients; 10 percent). One patient (3 percent) had Grade 4 ALT or AST increases.
Data also showed that treatment with IPI-145 led to decreases in serum levels of cytokines and chemokines known to play important roles in lymphocyte trafficking and function, further supporting the rationale that inhibiting PI3K-delta and PI3K-gamma has the potential to provide a therapeutic benefit for T-cell lymphoma as well as other blood cancers.
The poster is available in the Publications Archive on Infinity’s website http://www.infi.com/product-candidates-publications.asp.
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.
Infinity has launched DUETTSTM, a worldwide investigation of IPI-145 in blood cancers. As part of the DUETTS program, Infinity is currently enrolling patients in DYNAMOTM, a Phase 2 monotherapy study designed to evaluate the safety and efficacy of IPI-145 in patients with refractory indolent non-Hodgkin lymphoma (iNHL) (ClinicalTrials.gov Identifier NCT01882803), and DUOTM, a Phase 3 monotherapy study designed to evaluate the safety and efficacy of IPI-145 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) (NCT02004522).
An investigator-sponsored Phase 1b, open-label study of IPI-145 in patients with B-cell NHL, CLL and T-cell lymphoma in combination with rituximab (a monoclonal antibody therapy), bendamustine (a chemotherapy) or both rituximab and bendamustine is also open for enrollment (NCT01871675).
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: 99
