Phase 2 Results of Rigel's R788 Show Clinical Benefit in Diffuse Large B-Cell Lymphoma and CLL
Dec 7, 2008 14:00:00 (ET)
SAN FRANCISCO, Dec 07, 2008 /PRNewswire-FirstCall via COMTEX/ -- Results of the Phase 2 clinical trial of R788 (fostamatinib disodium) in patients with relapsed or refractory B-Cell non-Hodgkin's lymphoma (NHL) will be presented today at a plenary session during the 50th Annual American Society of Hematology (ASH) Meeting. The results affirm preliminary reports that Rigel's oral Syk inhibitor is well-tolerated by these patients and shows therapeutic benefit in patients suffering from diffuse large B-Cell lymphoma (DLBCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Rigel will host a conference call today at 4:00 p.m. PST to discuss these results (see conference call details below).
"Despite the fact that the patients enrolled in this trial had advanced disease and had failed treatment with marketed therapies, a significant number of them were particularly responsive to Syk inhibition with R788," said Jonathan Friedberg, M.D., M.S.Sc., Associate Professor of Medicine, James P. Wilmot Cancer Center, University of Rochester and lead investigator for the clinical trial. "I am encouraged by this data and look forward to conducting additional trials of R788, particularly in patients with DLBCL and CLL/SLL types of non-Hodgkin's lymphomas," he added.
Phase 2 Results: R788 in NHL Patients - 200 mg bid
Patients Overall % Patients
NHL Type (total n=68) Response Responding
DLBCL 23 5 22%
Follicular NHL 21 2 10%
Other NHL* 24
- CLL/SLL 11 6 55%
- MCL 9 1 11%
* Other NHL patients included 11 with CLL/SLL, 9 with Mantle cell NHL, 1
with Lymphoplasmacytic NHL and 3 with MALT/MZL. The 4 patients with
Lymphoplasmacytic and MALT are not referenced in the above table as
they did not show a response to treatment.
Clinical Trial Design
This clinical trial was conducted in two Phases. Phase 1 included a small group of patients and resulted in the selection of the dosing regimen employed in Phase 2. Nearly equal numbers of patients were enrolled in the three Phase 2 groups that included, respectively: DLBCL, follicular lymphoma (FL) and other non-Hodgkin's lymphomas (specifically CLL/SLL, MCL, MALT, marginal zone, and lymphoplasmacytic). Prior to enrollment in the R788 trial, all patients enrolled in the clinical trial had received various standard-of-care treatments for their disease, including combination chemotherapy, and had failed to respond to those therapies or suffered a relapse of the disease. A total of 68 patients received 200 mg PO bid (orally, twice daily) of R788 until disease progression occurred. Response to treatment was evaluated using standard NHL response criteria (The Cheson Criteria). Treatment-related adverse events included cytopenias, fatigue, diarrhea/abdominal discomfort and hypertension. Most adverse events were mild to moderate and were reversible. Four patients are continuing to receive R788, including 2 from the CLL/SLL group and 1 from the DLBCL group.
B-Cell Lymphoma and Syk Inhibition
Lymphoma affects an estimated 500,000 people in the United States, with 332,000 of them suffering from non-Hodgkin's lymphoma. Diffuse large B-cell lymphoma is the most common type of NHL and is generally categorized as aggressive, marked by rapidly growing tumors in the lymph nodes, spleen, liver, bone marrow and other organs. A variety of treatment options for NHL exist, including chemotherapy and radiation, but the five-year survival rate for NHL patients is estimated to be around 50%. Even for those who respond to treatment, recurrence of the disease is common.
A growing field of research on the cellular signaling associated with these lymphomas indicates that inhibiting Syk (spleen tyrosine kinase) in aberrant cells may control spread of the disease. Two additional research studies on the topic are also being presented at the ASH meeting. They are: Abstract 377, entitled "BCR, Signaling Diversity in Human Lymphoma B Cells Correlates with Follicular Lymphoma Patient Clinical Outcomes" and Abstract 802, entitled "BCL-6 Regulates Tonic BCR Signaling in Diffuse Large B-Cell Lymphomas." Further information on R788 in B-cell lymphoma is available at Rigel's website: rigel.com . |
