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|Infinity Reports Updated Phase 1 Data Showing Encouraging Clinical Activity of IPI-145 in Chronic Lymphocytic Leukemia at ASCO Annual Meeting|
– 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 –
“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
“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
IPI-145 Data Presented at
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
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
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
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.
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.
This press release contains forward-looking statements within the
meaning of The Private Securities Litigation Reform Act of 1995. Such
forward-looking statements include those regarding the Company’s
expectations about: its ability to execute on its strategic plans; plans
to initiate additional clinical trials; and the therapeutic potential of
PI3K inhibition, IPI-145 and IPI-443. Such statements are subject to
numerous important factors, risks and uncertainties that may cause
actual events or results to differ materially from the company’s current
expectations. For example, there can be no guarantee that Infinity will
report data in the time frames it has estimated, that any product
candidate Infinity is developing will successfully complete necessary
preclinical and clinical development phases, or that development of any
of Infinity’s product candidates will continue. Further, there can be no
guarantee that any positive developments in Infinity’s product portfolio
will result in stock price appreciation. Management’s expectations and,
therefore, any forward-looking statements in this press release could
also be affected by risks and uncertainties relating to a number of
other factors, including the following: Infinity’s results of clinical
trials and preclinical studies, including subsequent analysis of
existing data and new data received from ongoing and future studies; the
content and timing of decisions made by the U.S.
1 Data reported as of the
2 Halleck M et al. (2008) Guidelines for the diagnosis and
treatment of chronic lymphocytic leukemia: A report from the
3 Grever et al. (2007) Comprehensive assessment of genetic and molecular features predicting outcome in patients with chronic lymphocytic leukemia: Results from the US intergroup phase III trial E2997. J Clin Oncol 25:799-804.
4 Weinberg RA (2007) Cytoplasmic signaling circuitry programs
many of the traits of cancer. In Jeffcock E, Zayatz E, and Mickey RK
(Eds.) The biology of cancer (pp. 179-183).