Date: 2015-12-07
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the American Society of Hematology (ASH) Annual Meeting in Orlando, Florida, USA from December 5-8, 2015
Company: Immunomedics (USA - NJ)
Product: IMMU-114
Action
mechanism: monoclonal antibody. IMMU-114, targets a human leukocyte transplantation antigen, or HLA-DR, which is a receptor located on the cell surface and whose role is to present foreign antigens to the immune system for the purpose of eliciting an immune response. HLA-DR is expressed by a large number of blood cancers at significantly IMMU-114 was created as an IgG4, a subclass of immunoglobulin that does not function by the usual effector-cell activities of antibodies, such as complement-dependent cytotoxicity, or CDC, and antibody-dependent cellular cytotoxicity, or ADCC. As a result, IMMU-114 does not rely on an intact immune system in the patient to kill tumor cells, but directly affects the signaling, metabolism and proliferation of the targeted cancer cells. Since ADCC and CDC are believed to play a major role in causing the side effects of antibody therapy, IMMU-114 is expected to be less toxic to patients.
higher levels than typical B-cell markers, including CD20, thus making it a prime target for antibody therapy. By targeting HLA-DR, a receptor that is different from CD20, CD22, CD30, and CD52 antigens inhibited by other antibodies in lymphoma and leukemia therapy, IMMU-114 may represent a new treatment option to combat these cancers.
Disease: non-hodgkin's lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, chronic lymphocytic leukemia, small lymphocytic lymphoma
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: IMMU-114 will be studied at different dose schedules and dose levels in order to assess the highest dose safely tolerated. IMMU-114 will be administered subcutaneously (under the skin). IMMU-114 will be given 1-2 times weekly for 3 weeks followed by one week of rest. This is considered one cycle. Treatment cycles will be repeated until toxicity or worsening of disease. (NCT01728207)
Latest
news: * On December 7, 2015, Immunomedics announced that 50% of patients showed objective evidence of treatment activity, including one patient with a complete response, in a Phase 1, first-in-man clinical study of the Company’s proprietary humanized antibody, IMMU-114, in patients with relapsed non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). The anti-HLA-DR antibody is being evaluated as a subcutaneous monotherapy in the dose escalation study. First results from this study were presented at the 2015 Annual Meeting of the American Society of Hematology by Dr. Deborah M Stephens at the Huntsman Cancer Institute,
University of Utah, Salt Lake City, UT. Seventeen patients with a median of 2 prior therapies (range 1 – 7) had been enrolled. All 17 patients had failed rituximab or other anti-CD20 antibody therapies. Ten patients in the initial dose-escalation phase of the study received 200 mg IMMU-114 injections once, twice, or thrice
weekly for the first 3 weeks of a 4-week cycle. All patients receive 2 consecutive treatment cycles, followed 4 weeks later by elective maintenance therapy.
While the maximum tolerated dose was not determined, with lack of toxicity and preliminary efficacy already observed at the two lowest dose levels, the twice-weekly dosing schedule was chosen for subsequent patients enrolled. Treatment response was assessed using 2007 IWG-NHL or 2008 IW-CLL criteria 4 weeks after cycle 2, then every 3 months until disease progression. At the time of analysis, ten patients were evaluable for treatment response. In total, five assessable patients had evidence of treatment response (stable disease, partial and
complete responses), including one patient with follicular lymphoma who reported a complete response and another with stable disease, as well as one patient with diffuse large B-cell lymphoma with a partial response and two patients with CLL having partial responses.
The presentation also included initial preclinical results showing how IMMU-114 could potentially improve the results of other agents used in the therapy of patients with CLL. Cell culture experiments with a CLL line showed that combining IMMU-114 with a Bruton kinase inhibitor, such as ibrutinib, or a PI3k inhibitor, such as idelalisib, could result in additive therapeutic effects.
