Hematology Meeting Reports 2008;2(5):78 SESSION V

C. Assaf Zanolimumab (HuMax-CD4®), a fully Skin Cancer Center Charité, human monoclonal in clinical Department of Dermatology and Allergy Charité development for cutaneous T-cell Universitätsmedizin-Berlin, Germany lymphoma

Zanolimumab (HuMax-CD4®; an objective response compared to Genmab, Copenhaven, Denmark) 15% with a dosage of 280 mg. The is a monoclonal human anti-CD4 response rate within the SS was antibody and specifically targets T- 20% for the patients who were helper cells as well as CD4+ CTCL treated with the higher dose and tumor cells and at a lower level 25% for the low dose. The median monocytes and macrophages. Due duration of response for the high- to the interference with the interac- dose levels was 81 weeks in the tion of the CD4 and the group of MF. The duration of major histocompatibility complex response for the two responding class II-molecule (MHC-II) this patients with SS was 61 weeks antibody is decreasing T-cell acti- (980 mg) and 8 weeks (280 mg). vation. In 2 phase II multicenter, These two studies with zanoli- prospective, open-label clinical tri- mumab give an appreciable effica- als the efficiency and safety of this cy in patients with CTCL and a anti-CD4 antibody was determined high response rate as well as par- in relapsed early and advanced tially durable responses. A phase staged CTCL patients. 38 patients III pivotal trial, in patients with with MF and 9 patients with SS MF (stage IB-IVB) or SS who are were treated intravenously with refractory or intolerant to zanolimumab at a dosage of 280 bexarotene and one other standard mg or 560 mg for early stage therapy is now running for regis- patients and with 280 mg or 980 tration. After the safety dose-esca- mg for advanced stage patients. lation part I (n=21), the part II of Overall responses could be seen in the study is currently running as an both patient groups. 13 cases of open label single arm mono-thera- MF and 2 cases of SS showed a py study where Zanolimumab is response. In the group of MF 56% administered i.v at a dose of 14 within the high-dose levels showed mg/kg, once weekly for 12 weeks.

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A. Hagenbeek Monoclonal (novel): Department of Hematology, humax-CD20, ofatumumab Academic Medical Center, Amsterdam, The Netherlands

Ofatumumab, the first fully response rate of 50% (13/26) was human anti-CD20 monoclonal achieved (Coiffier et al., 2008). antibody, targets a novel epitope No complete remissions were of the CD20 molecule on B-cells observed. Most patients showed and releases only very slowly more than 50% decrease in lymph from the target compared with rit- node size from week 4, which was uximab. The antibody is generat- sustained until week 15. The ed via transgenic mouse and median percentage reduction hybridoma technology. Compared from baseline of malignant CD5+ with , ofatumumab has CD19+ B-cells in the peripheral similar ADCC, but stronger CDC, blood was 97%, which lasted until even to lymphoma cells with a week 24. Infections were experi- low CD20 antigen density and a enced by 17/33 patients (51%), high number of CD55 and CD59 88% of these were of grade 1/2. complement inhibitory molecules One event of interstitial pneumo- present in the cell membrane. In nia was fatal. addition, ofatumumab kills fresh In relapsed/refractory follicular B-CLL cells resistant to ritux- lymphoma, 4 dose groups of 10 imab. In the cynomolgus monkey patients each received 4 weekly model, the ofatumumab-depletion infusions of 300, 500, 700 or 1000 of B-cells from peripheral blood mg. Patients had a median of 2 and lymph nodes lasted longer prior FL therapies. No safety con- than the depletion induced by rit- cerns or maximum tolerated dose uximab. were identified. Treatment caused Given the above, ofatumumab immediate and profound B-cell has the potential to treat B-cell depletion lasting up to 1 year and malignancies with low CD20 65% of patients reverted to a neg- expression, such as B-CLL and ative bcl2 status. Clinical rituximab-refractory follicular response rates range from 20- lymphoma. 63%, without a clear-cut dose- Indeed, in a multicenter dose- response relationship. Median escalating study including 33 time to progression for all patients with relapsed or refracto- patients/responders was 8.8/32.6 ry CLL (Binet stage B: 67%; months and median duration of median number of previous treat- response was 29.9 months ments: 3). The response rate in the (Hagenbeek et al., 2008). cohort receiving the highest doses Based on these promising data, (first infusion 500 mg, followed several new ofatumumab trials by 3 infusions of 2000 mg each, were launched, e.g. in CLL given at weekly intervals), a addressing the efficacy in patients

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