The FINANCIAL — Pharmacyclics, Inc. (Nasdaq: PCYC) on December 6 announced interim results from a Phase I/II study showing safety and clinical activity in patients with relapsed / recurrent non-Hodgkin's Lymphoma (NHL) treated with its HDAC inhibitor PCI-24781 as a single agent.
The data were presented today at the 51st ASH Annual Meeting being held in New Orleans, LA (Abstract # 2726).
PCI-24781 is an oral pan-HDAC inhibitor which is currently in multiple clinical trials for solid and hematological malignancies (PCYC-0401 single center, solid tumor cancer patients IV administered drug; PCYC-0402 multi-center, solid cancer patients orally administered; PCYC-0403 multicenter, lymphoma cancer patients orally administered). This compound, which has been optimized for the best combination of potency and pharmacokinetics (PK), has potent anti-tumor activity in a variety of preclinical tumor models (Buggy et al Mol Cancer Ther 5:1309-1317, 2006) and has also demonstrated safety and clinical benefit in human solid tumors (Undevia et al, ASCO 2008).
In a review of the clinical data at the end of the Phase I dose-escalation portion of the current lymphoma trial, it was revealed that PCI-24781 has shown strong signs of efficacy with minimal toxicity as a single agent in lymphoma, with 1 Complete Response (follicular lymphoma), 4 Partial Responses (2 follicular lymphoma, 1 diffuse large B-cell lymphoma, 1 mantle cell lymphoma) and 6 Stable Disease in 16 patients evaluated for response (after 2 cycles). Partial Response is defined as a 50% reduction in tumor size. The Overall Response Rate (Partial and Complete Response) has been 31%, with responses being observed in each of the four cohorts. Of 4 follicular lymphoma patients evaluated in this trial, 3 had objective responses (1 Complete Response and 2 Partial Responses).
The patients enrolled in this trial were heavily pre-treated (mean = 3 prior treatments) and had diverse histologies, including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma. A total of 25 patients were enrolled, with 5 still on study after 5-10 cycles of treatment. Dose limiting toxicities observed in this trial were reversible thrombocytopenia (n=3), diarrhea (n=1) and renal failure (n=1). Of note, no pericarditis, pericardial effusion, or QT prolongation were seen at any dose level of PCI-24781. The dose and schedule have been optimized for the Phase II portion of the study.
"At completion of the Phase I stage of this clinical trial, PCI-24781 showed encouraging clinical activity as a mono-therapy in relapsed/refractory non-Hodgkin's lymphoma including several complete and partial remissions. Furthermore, due to its favorable side effect profile, pharmacokinetics, and large therapeutic window, it has the potential to be a class leader in the competitive HDAC inhibitor arena," said Dr. Andrew Evens, principal investigator of the study, and Assistant Professor of Medicine and Director of Translational Therapeutics in the Division of Hematology/Oncology at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago.
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