– Early Data Show that IPI-145 Is Well Tolerated, with a 55 Percent Partial Response Rate in Chronic Lymphocytic Leukemia –
– Rapid Onset of Clinical Activity Observed, with a Median Time to Response of 1.9 Months –
– Company Announces Initiation of New Phase 1 Expansion Cohort in Newly Diagnosed, High-Risk Chronic Lymphocytic Leukemia –
CHICAGO, IL, USA I June 2, 2013 I Infinity Pharmaceuticals, Inc. (INFI) today announced updated Phase 1 data from an ongoing study of IPI-145, its potent, oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), a potentially fatal hematologic malignancy, or blood cancer. Data from the study showed that IPI-145 was well tolerated, with a rapid onset of clinical activity. These findings were presented today at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting. Based on the tolerability and activity profile of IPI-145 observed to date, Infinity also today announced that it has initiated a new expansion cohort within its ongoing Phase 1 study to evaluate the safety, activity and pharmacokinetics (PK) of IPI-145 dosed at 25 mg twice daily (BID) as treatment for patients with newly diagnosed, high-risk CLL.
“The early data from this Phase 1 study of IPI-145 continue to be encouraging. IPI-145 was well tolerated and showed rapid clinical activity in patients with CLL, with a median time to response of 1.9 months,” commented Ian Flinn, M.D., Ph.D., director, hematologic malignancies program, Sarah Cannon Research Institute, and an investigator for the trial. “These data support continued development of IPI-145, and I look forward to further evaluation of this investigational drug in patients with both advanced and newly diagnosed CLL.”
“The data presented today reinforce Infinity’s enthusiasm for IPI-145. We believe that the potency and activity of IPI-145 against both PI3K-delta and PI3K-gamma contribute to its potential to become the best-in-class PI3K inhibitor for the treatment of blood cancers,” stated Julian Adams, Ph.D., president of research and development at Infinity. “These data support the initiation of an additional expansion cohort to evaluate the potential of IPI-145 in newly diagnosed, high-risk patients with CLL. Beyond this Phase 1 study, Infinity is moving rapidly to advance the development of IPI-145 and is planning to initiate at least two company-sponsored studies of IPI-145 in hematologic malignancies this year.”
IPI-145 Data Presented at ASCO in Patients with CLL
The presentation, “Preliminary safety and efficacy of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with relapsed/refractory CLL” (Abstract #7070), includes 117 patients in the total safety population, of which 34 patients with CLL were evaluable for safety and 22 were evaluable for clinical activity.1 All patients enrolled in the study had advanced disease and had progressed during or were refractory to, intolerant of, or ineligible for established therapy. CLL patients enrolled in the study had a median of four prior systemic therapies (range:one – nine), and 26 of the 34 patients (76 percent) had at least three prior systemic therapies.
Safety and Pharmacokinetics
Data presented today showed that IPI-145 was well tolerated, with a safety profile consistent with co-morbidities seen in patients with advanced hematologic malignancies. There have been no dose-related trends in adverse events at the doses evaluated from 8 mg BID to 75 mg BID in either the total safety population or in patients with CLL. Adverse events were primarily managed by dose interruptions and reductions. Among CLL patients enrolled in the study, the most frequent Grade 3/4 adverse event was neutropenia. Grade 3 and Grade 4 neutropenia occurred in five (15 percent of) and eight (24 percent of) patients, respectively. The majority of neutropenia observed did not require dose reductions. Grade 3 elevations in transaminases (ALT/AST) occurred in two (6 percent of) patients. Sixty-five percent of CLL patients remain on study.
Data also showed that IPI-145 is rapidly absorbed and demonstrates a linear PK profile through 75 mg BID, with complete inhibition of PI3K-delta and at least 50 percent inhibition of PI3K-gamma at doses ≥ 25 mg BID. IPI-145 also led to profound and sustained inhibition of AKT phosphorylation, a marker of PI3K activation, as well as reductions in several cytokines and chemokines that are known to be important in lymphocyte trafficking and function.
Clinical Activity in CLL
IPI-145 is clinically active in patients with CLL, with a rapid onset of response as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) IWC criteria2 and a rapid resolution of lymphocytosis. Among the 22 patients evaluable for response, there were 12 partial responses (55 percent IWCLL partial response rate) and an additional seven nodal responses. The median time to response was 1.9 months (range:1.8 – 5.6 months). Ten of the 12 partial responses were at doses ≤ 25 mg BID.
The trial also included patients with a deletion of the short arm of chromosome 17 (17p del) or with p53 mutations. Patients with CLL with a 17p del or p53 mutations generally have a poor response to chemotherapy and worse prognosis.3 Among four patients evaluable with 17p del, there were two partial responses, one stable disease, and one progression due to Richter’s transformation. Among six patients evaluable with a p53 mutation, there were four partial responses and two nodal responses.
This poster was presented in McCormick Place, S Hall A2, in Chicago, Illinois, and may also be found in the Publications Archive on Infinity’s website http://www.infi.com/product-candidates-publications.asp.
New Expansion Cohort in Phase 1 Study of IPI-145 in Advanced Hematologic Malignancies
Based on the tolerability and activity observed in the ongoing Phase 1 study of IPI-145 in patients with advanced hematologic malignancies, a new expansion cohort within this study is open for enrollment. This cohort is designed to evaluate the safety, activity and PK of IPI-145 dosed at 25 mg BID in approximately 30 newly diagnosed patients who have high-risk CLL, defined as patients over the age of 65 or with a 17p deletion or p53 mutations.
About the Phase 1 Trial of IPI-145 in Advanced Hematologic Malignancies
The Phase 1, open-label, dose-escalation trial of IPI-145 is designed to evaluate the safety, PK and clinical activity of IPI-145 administered orally BID in patients with advanced hematologic malignancies. The dose-escalation portion of the study is complete, with the maximum tolerated dose defined at 75 mg BID. Infinity is continuing to evaluate IPI-145 in the following seven expansion cohorts:
25 mg BID expansion cohorts
1. Relapsed/refractory CLL, indolent non-Hodgkin lymphoma (iNHL) and mantle cell lymphoma (MCL)
2. Treatment-naïve CLL in high-risk patients (over age 65 or having a 17p del or p53 mutations)
75 mg BID expansion cohorts
1. Relapsed/refractory CLL, iNHL and MCL
2. T-cell lymphomas
3. Aggressive B-cell lymphomas
4. Myeloid neoplasms
5. Acute lymphoblastic leukemia
About Infinity’s PI3K Program in Blood Cancers
Infinity is developing IPI-145, a potent, oral inhibitor of Class I phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma. The PI3Ks are a family of enzymes involved in multiple cellular functions, including cell proliferation and survival, cell differentiation, cell migration and immunity.4 The PI3K-delta and PI3K-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 and inflammatory diseases.
IPI-145, Infinity’s lead product candidate, is currently progressing in a Phase 1 study in patients with advanced hematologic malignancies. An investigator-sponsored Phase 1b, open-label, dose-escalation 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.
Additionally, Infinity is conducting preclinical studies of IPI-443, its second oral PI3K-delta and PI3K-gamma inhibitor. IPI-443 has a distinct biochemical profile from IPI-145 and also has the potential to treat hematologic malignancies and inflammatory diseases.
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. Infinity’s programs focused on the inhibition of phosphoinositide-3-kinase and heat shock protein 90 are evidence of its innovative approach to drug discovery and development. For more information on Infinity, please refer to the company’s website at www.infi.com.
SOURCE: Infinity Pharmaceuticals
Post Views: 153
– Early Data Show that IPI-145 Is Well Tolerated, with a 55 Percent Partial Response Rate in Chronic Lymphocytic Leukemia –
– Rapid Onset of Clinical Activity Observed, with a Median Time to Response of 1.9 Months –
– Company Announces Initiation of New Phase 1 Expansion Cohort in Newly Diagnosed, High-Risk Chronic Lymphocytic Leukemia –
CHICAGO, IL, USA I June 2, 2013 I Infinity Pharmaceuticals, Inc. (INFI) today announced updated Phase 1 data from an ongoing study of IPI-145, its potent, oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), a potentially fatal hematologic malignancy, or blood cancer. Data from the study showed that IPI-145 was well tolerated, with a rapid onset of clinical activity. These findings were presented today at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting. Based on the tolerability and activity profile of IPI-145 observed to date, Infinity also today announced that it has initiated a new expansion cohort within its ongoing Phase 1 study to evaluate the safety, activity and pharmacokinetics (PK) of IPI-145 dosed at 25 mg twice daily (BID) as treatment for patients with newly diagnosed, high-risk CLL.
“The early data from this Phase 1 study of IPI-145 continue to be encouraging. IPI-145 was well tolerated and showed rapid clinical activity in patients with CLL, with a median time to response of 1.9 months,” commented Ian Flinn, M.D., Ph.D., director, hematologic malignancies program, Sarah Cannon Research Institute, and an investigator for the trial. “These data support continued development of IPI-145, and I look forward to further evaluation of this investigational drug in patients with both advanced and newly diagnosed CLL.”
“The data presented today reinforce Infinity’s enthusiasm for IPI-145. We believe that the potency and activity of IPI-145 against both PI3K-delta and PI3K-gamma contribute to its potential to become the best-in-class PI3K inhibitor for the treatment of blood cancers,” stated Julian Adams, Ph.D., president of research and development at Infinity. “These data support the initiation of an additional expansion cohort to evaluate the potential of IPI-145 in newly diagnosed, high-risk patients with CLL. Beyond this Phase 1 study, Infinity is moving rapidly to advance the development of IPI-145 and is planning to initiate at least two company-sponsored studies of IPI-145 in hematologic malignancies this year.”
IPI-145 Data Presented at ASCO in Patients with CLL
The presentation, “Preliminary safety and efficacy of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with relapsed/refractory CLL” (Abstract #7070), includes 117 patients in the total safety population, of which 34 patients with CLL were evaluable for safety and 22 were evaluable for clinical activity.1 All patients enrolled in the study had advanced disease and had progressed during or were refractory to, intolerant of, or ineligible for established therapy. CLL patients enrolled in the study had a median of four prior systemic therapies (range:one – nine), and 26 of the 34 patients (76 percent) had at least three prior systemic therapies.
Safety and Pharmacokinetics
Data presented today showed that IPI-145 was well tolerated, with a safety profile consistent with co-morbidities seen in patients with advanced hematologic malignancies. There have been no dose-related trends in adverse events at the doses evaluated from 8 mg BID to 75 mg BID in either the total safety population or in patients with CLL. Adverse events were primarily managed by dose interruptions and reductions. Among CLL patients enrolled in the study, the most frequent Grade 3/4 adverse event was neutropenia. Grade 3 and Grade 4 neutropenia occurred in five (15 percent of) and eight (24 percent of) patients, respectively. The majority of neutropenia observed did not require dose reductions. Grade 3 elevations in transaminases (ALT/AST) occurred in two (6 percent of) patients. Sixty-five percent of CLL patients remain on study.
Data also showed that IPI-145 is rapidly absorbed and demonstrates a linear PK profile through 75 mg BID, with complete inhibition of PI3K-delta and at least 50 percent inhibition of PI3K-gamma at doses ≥ 25 mg BID. IPI-145 also led to profound and sustained inhibition of AKT phosphorylation, a marker of PI3K activation, as well as reductions in several cytokines and chemokines that are known to be important in lymphocyte trafficking and function.
Clinical Activity in CLL
IPI-145 is clinically active in patients with CLL, with a rapid onset of response as defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) IWC criteria2 and a rapid resolution of lymphocytosis. Among the 22 patients evaluable for response, there were 12 partial responses (55 percent IWCLL partial response rate) and an additional seven nodal responses. The median time to response was 1.9 months (range:1.8 – 5.6 months). Ten of the 12 partial responses were at doses ≤ 25 mg BID.
The trial also included patients with a deletion of the short arm of chromosome 17 (17p del) or with p53 mutations. Patients with CLL with a 17p del or p53 mutations generally have a poor response to chemotherapy and worse prognosis.3 Among four patients evaluable with 17p del, there were two partial responses, one stable disease, and one progression due to Richter’s transformation. Among six patients evaluable with a p53 mutation, there were four partial responses and two nodal responses.
This poster was presented in McCormick Place, S Hall A2, in Chicago, Illinois, and may also be found in the Publications Archive on Infinity’s website http://www.infi.com/product-candidates-publications.asp.
New Expansion Cohort in Phase 1 Study of IPI-145 in Advanced Hematologic Malignancies
Based on the tolerability and activity observed in the ongoing Phase 1 study of IPI-145 in patients with advanced hematologic malignancies, a new expansion cohort within this study is open for enrollment. This cohort is designed to evaluate the safety, activity and PK of IPI-145 dosed at 25 mg BID in approximately 30 newly diagnosed patients who have high-risk CLL, defined as patients over the age of 65 or with a 17p deletion or p53 mutations.
About the Phase 1 Trial of IPI-145 in Advanced Hematologic Malignancies
The Phase 1, open-label, dose-escalation trial of IPI-145 is designed to evaluate the safety, PK and clinical activity of IPI-145 administered orally BID in patients with advanced hematologic malignancies. The dose-escalation portion of the study is complete, with the maximum tolerated dose defined at 75 mg BID. Infinity is continuing to evaluate IPI-145 in the following seven expansion cohorts:
25 mg BID expansion cohorts
1. Relapsed/refractory CLL, indolent non-Hodgkin lymphoma (iNHL) and mantle cell lymphoma (MCL)
2. Treatment-naïve CLL in high-risk patients (over age 65 or having a 17p del or p53 mutations)
75 mg BID expansion cohorts
1. Relapsed/refractory CLL, iNHL and MCL
2. T-cell lymphomas
3. Aggressive B-cell lymphomas
4. Myeloid neoplasms
5. Acute lymphoblastic leukemia
About Infinity’s PI3K Program in Blood Cancers
Infinity is developing IPI-145, a potent, oral inhibitor of Class I phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma. The PI3Ks are a family of enzymes involved in multiple cellular functions, including cell proliferation and survival, cell differentiation, cell migration and immunity.4 The PI3K-delta and PI3K-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 and inflammatory diseases.
IPI-145, Infinity’s lead product candidate, is currently progressing in a Phase 1 study in patients with advanced hematologic malignancies. An investigator-sponsored Phase 1b, open-label, dose-escalation 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.
Additionally, Infinity is conducting preclinical studies of IPI-443, its second oral PI3K-delta and PI3K-gamma inhibitor. IPI-443 has a distinct biochemical profile from IPI-145 and also has the potential to treat hematologic malignancies and inflammatory diseases.
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. Infinity’s programs focused on the inhibition of phosphoinositide-3-kinase and heat shock protein 90 are evidence of its innovative approach to drug discovery and development. For more information on Infinity, please refer to the company’s website at www.infi.com.
SOURCE: Infinity Pharmaceuticals
Post Views: 153
