New Regimens Combine Radioimmunotherapy With Yttrium-90-labeled Epratuzumab and Anti-CD20 Immunotherapy
Two Studies Updated at 2012 Annual Meeting of American Society of Hematology (ASH) Including an Oral Presentation
ATLANTA, Dec. 11, 2012 (GLOBE NEWSWIRE) -- Immunomedics, Inc. (Nasdaq:IMMU), a biopharmaceutical company primarily focused on the development of monoclonal antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases, today reported that small, repeated doses of epratuzumab labeled with the radioisotope, yttrium-90 (90Y), demonstrated therapeutic activity in 2 clinical trials in patients with aggressive non-Hodgkin lymphoma (NHL).
Epratuzumab is a humanized antibody that binds to the CD22 receptor on B cells. In various clinical trials, epratuzumab was found to be active as an unlabeled antibody in patients with NHL or lupus. Previous clinical studies have also demonstrated that repeated administration of small doses of 90Y-epratuzumab are tolerable in NHL patients and produced high rates of durable responses.
Despite recent advances in the use of antibody for the management of NHL, aggressive NHLs have proven to be more resistant to currently approved antibody therapies unless they are combined with chemotherapy. Diffuse large B-cell lymphoma (DLCBL) is the most common type of aggressive NHL, with approximately 20,000 new patients diagnosed each year in the United States. The standard-of-care for DLBCL is combining the anti-CD20 antibody, rituximab, with the CHOP chemotherapy regimen, or R-CHOP. However, elderly patients who fail R-CHOP have a poor outcome. Due to advanced age, chemo-resistant disease, and/or concurrent co-morbid medical conditions, a significant percentage of these patients are not eligible for high-dose salvage therapy or stem cell transplant. Consequently, there is a need for alternative therapy for high-risk patients with a lower chance of being cured with standard R-CHOP.
An innovative approach for NHL therapy that the Company and its outside collaborators are developing is to combine antibody-directed radiation therapy using 90Y-epratuzumab with antibody therapy targeting a different antigen. Since the two antibodies bind to two distinct antigens and do not cross-block each other, this concept may offer more synergy than current NHL radioimmunotherapy that employs unlabeled antibody targeting the same B-cell antigen.
Updated results from a multicenter Phase II trial sponsored by the French LYSA study group were reported in an oral presentation at this year's ASH Annual Meeting by Pierre Soubeyran, MD, PhD, of the Bergonié Cancer Institut, Bordeaux, France. The goal of this open-label study is to evaluate 90Y-epratuzumab given in small doses as consolidation therapy after R-CHOP in previously untreated elderly patients with advanced DLBCL. Primary end-point of the study is 2-year event-free survival (EFS).
At the time of reporting, a total of 75 patients between the ages of 60 and 80 years had been enrolled to receive 6 cycles of R-CHOP therapy, with 61 patients eligible for 2 consolidation treatments of 90Y-epratuzumab at 15 mCi/m2.
Using the 1999 International Workshop for Response Criteria for NHL, the overall response rate (ORR) after 6 cycles of R-CHOP therapy was 94.6% (71/75), with 52 patients (69.3%) achieving a complete or unconfirmed complete response (CR/CRu) and 19 patients (25.3%) reporting a partial response (PR). At a median follow-up of 24 months (range from 1 - 46), 18 patients experienced lymphoma progression and/or related death, yielding an estimated 2-year EFS of 73.3% (60.7 - 82.5%) and an estimated 2-year overall survival (OS) of 83.2% (71.4 - 90.4%).
For the 61 patients who received the 2 consolidation 90Y-epratuzumab treatments, ORR was 91.8% (56/61), with 50 patients (81.9%) achieving a CR/CRu. Eight of 16 patients (50.0%) who had less than a CR/CRu with R-CHOP converted to CR/CRu after receiving radiolabeled epratuzumab. Among these 61 patients, 12 experienced progression and/or related death, yielding an estimated 2-year EFS of 78.7% (65.1 - 87.4%) and an estimated 2-year OS of 90.1% (77.7 - 95.8%).
Separately, the Company is investigating a combination of 90Y-epratuzumab and its second-generation, humanized anti-CD20 antibody, veltuzumab, in patients with relapsed aggressive NHL. Michael B Tomblyn, MD, of H. Lee Moffitt Cancer Center, Tampa, FL, presented updated results at the same ASH medical conference, with clinical research sites from Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN; Helen F Graham Cancer Center, Newark, DE; Weill Cornell Medical College, New York, NY; and Indiana University Health Center for Cancer Care, Goshen, IN, participating in this Phase I, open-label study.
Results from 18 patients with various types of aggressive NHL who had failed 1 or more prior standard therapies were reported at the conference. The 90Y dose was repeatedly de-escalated from 15 (N=3) to 12 (N=3), 9 (N=6), and currently 6 (N=6) mCi/m2 due to hematologic dose-limiting toxicities. Otherwise, treatment was well-tolerated with no infusion reactions.
The overall objective response rate among 17 patients who have had treatment response assessments was 53%, including one DLBCL patient (6%) with a CR continuing 12 months later. The combination is active in all NHL subgroups and across 90Y dose levels. At the maximum tolerated dose of 6 mCi/m2 x 2, 5 of 6 patients (83%) achieved PRs.
"We are pleased with these encouraging early efficacy results," remarked Cynthia L. Sullivan, President and Chief Executive Officer of Immunomedics. "We will continue to develop this combination of 90Y-epratuzumab and anti-CD20 antibody therapy to hopefully become a new treatment regimen for NHL," Ms. Sullivan added.
This study was supported in part by Award Number R44CA139668 from the National Cancer Institute. The content is solely the responsibility of the Company and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.
Immunomedics is a New Jersey-based biopharmaceutical company primarily focused on the development of monoclonal antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases. We have developed a number of advanced proprietary technologies that allow us to create humanized antibodies that can be used either alone in unlabeled or "naked" form, or conjugated with radioactive isotopes, chemotherapeutics, cytokines or toxins, in each case to create highly targeted agents. Using these technologies, we have built a pipeline of therapeutic product candidates that utilize several different mechanisms of action. We also have a majority ownership in IBC Pharmaceuticals, Inc., which is developing a novel DOCK-AND-LOCK™ (DNL™) method with us for making fusion proteins and multifunctional antibodies, and a new method of delivering imaging and therapeutic agents selectively to disease, especially different solid cancers (colorectal, lung, pancreas, etc.), by proprietary, antibody-based, pretargeting methods. We believe that our portfolio of intellectual property, which includes approximately 209 active patents in the United States and more than 400 foreign patents, protects our product candidates and technologies. For additional information on us, please visit our website at www.immunomedics.com. The information on our website does not, however, form a part of this press release.
This release, in addition to historical information, may contain forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Such statements, including statements regarding clinical trials, out-licensing arrangements (including the timing and amount of contingent payments), forecasts of future operating results, potential collaborations, and capital raising activities, involve significant risks and uncertainties and actual results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, risks associated with any cash payment that the Company might receive in connection with a sublicense involving a third party and UCB, which is not within the Company's control, new product development (including clinical trials outcome and regulatory requirements/actions), our dependence on our licensing partners for the further development of epratuzumab and veltuzumab for non-cancer indications, competitive risks to marketed products and availability of required financing and other sources of funds on acceptable terms, if at all, as well as the risks discussed in the Company's filings with the Securities and Exchange Commission. The Company is not under any obligation, and the Company expressly disclaims any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise.
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