Genmab

69 Ofatumumab With IVAC Salvage Chemotherapy in Diffuse Large B Cell Lymphoma Patients (PLRG8) This study is not yet open for participant recruitment. Verified on November 2011 by Polish Lymphoma Research Group First Received on November 14, 2011. Last Updated on November 28, 2011 History of Changes Sponsor: Polish Lymphoma Research Group Information provided by (Responsible Party): Polish Lymphoma Research Group ClinicalTrials.gov Identifier: NCT01481272

ja okay

Ofatumumab studie 68 The main purpose of this study is to examine how two separate groups of 17p deletion CLL participants respond to sequential treatment with this particular combination of drugs. The two groups are those participants who have previously received treatment for their CLL and those who have not yet received any treatment. The combination of drugs is Ofatumumab and High-Dose Methylprednisolone (HDMP) first followed by Ofatumumab and Alemtuzumab. All three drugs are FDA approved and have known activity in treating 17p CLL. We hope that by combining these drugs together in this study, they will have more benefit than each one alone and that the subjects' CLL will be significantly impacted. Sponsor: Dana-Farber Cancer Institute Collaborators: National Comprehensive Cancer Network GlaxoSmithKline

Basel, Switzerland, 25 October 2011: Today, Lonza announces a new development and manufacturing agreement with Genmab A/S. This agreement secures a development and cGMP manufacturing plan for Genmab to produce a novel ADC product targeting tissue factor (TF), a protein involved in tumor signalling and angiogenesis that is highly expressed on solid tumors. The use of ADCs as therapeutic agents is becoming an important therapeutic approach for the treatment of various cancers. This project utilizes Lonza’s experts in both antibody production and drug conjugation, providing a harmonized solution for Genmab’s technology. Lonza will initiate process development and cGMP manufacturing for Genmab’s monoclonal antibody HuMax-TF in its Slough, UK facility. This antibody has been expressed by Genmab A/S in Lonza’s GS Gene Expression System. The naked antibody will be conjugated by Lonza at its ADC plant in Visp, CH to a cytotoxic drug in order to form the antibody drug conjugate HuMax-TF.

så det kunne da godt være at det var i næste uge jeg skulle købe de sidste 17k,

RRMS forsøget har længe været lovet påbegyndt og er af meget stor betydning for Genmabs kurs på den lange bane. RRMS indikationen kan blive en MEGA-stor blockbuster for GSK/Genmab. Forløber forsøget tilfredstilende ændres forsøget til et fase 3 og yderligere pts optages i den eller de forsøgsarme der er succes i. Men tålmodighed er en dyd

Hey Leo,jeg har en hel del forskellige "lorteaktier "og venter forgæves på explodingday ,hvornår kommer den ?????

Ofatumumab er nået til 67, men jeg har mistet overblikket. Der sker meget for tiden. Tror nok, at et af disse er nr. 67... Not yet recruiting Bendamustine in Combination With Ofatumumab, Carboplatin and Etoposide for Refractory or Relapsed Aggressive B-Cell Lymphomas Condition: Non-Hodgkin's Lymphoma Interventions: Drug: Bendamustine; Drug: Ofatumumab; Drug: Carboplatin; Drug: Etoposide; Procedure: CT Scan; Procedure: PET Scan; Genetic: Stem Cell Transplant (STC) Last Updated Date: October 20, 2011 Not yet recruiting Study of Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisone (CHOP) With Ofatumumab in Patients With Richter's Syndrome Condition: Richter's Syndrome Intervention: Drug: Ofatumumab Last Updated Date: October 21, 2010

Dette er vist nr.66 Ofatumumab is a novel IgG1? lytic monoclonal antibody (mAb) that specifically binds to the human CD20 antigen of which expression is restricted to B lymphocytes from the pre-B cell stage to the plasmacytoid immunoblast stage only. A recent trial with an anti-CD20 mAb (rituximab) demonstrated that targeting B-cells reduces the number of gadolinium-enhancing (GdE) T1 lesions and the relapse rate in relapsing-remitting multiple sclerosis (RRMS). Ofatumumab has been shown to be both well tolerated and efficacious in several indications, including a small, placebo-controlled trial in RRMS using an intravenous (IV) formulation. This double-blind, placebo-controlled, parallel-group study will investigate the safety and efficacy of a subcutaneous formulation of ofatumumab in the treatment of subjects with RRMS. The primary objective of the study is to investigate the efficacy as assessed by magnetic resonance imaging. Other objectives will include evaluation of tolerability/safety, dose-response relationship, pharmacokinetics, pharmacodynamics, exposure-response, as well as other clinical endpoints.

Ofatumumab studie 65: A good proportion of patients with chronic lymphocytic leukemia (CLL) can be managed effectively with palliative chemotherapy. However, there is a group of younger patients with poor risk disease whose life expectancy is significantly reduced. As a result, reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (allo-HCT) has been investigated as a potentially curative procedure. Recently, the European Group for Blood and Marrow Transplantation (EBMT) published a set of guidelines suggesting situations where allo-HCT might be considered a therapeutic option for CLL patients. Their conclusions were that allo-HCT was reasonable for younger CLL patients refractory to fludarabine, relapsing within two years of intensive treatment, or with p53 abnormalities requiring treatment. However, the results with RIC allo-HCT are not entirely satisfactory, and progression-free survival after allo-HCT revolves around 35-40% at 3-5 years following allo-HCT. This is due to non-relapse mortality, which is significantly associated with the development of graft-versus-host disease (GVHD), but also due to disease relapse. These relapses may occur early in the course of the transplantation, like any other hematological malignancy, but late relapses have also been reported. Several strategies have been tested in order to improve these results. The anti-CD20 monoclonal antibody rituximab, given concomitantly with allo-HCT or donor lymphocyte infusions, may reduce graft-versus-host disease and facilitate disease control. This may be due, not only to direct cytotoxicity, but also to modulation of GVHD and the graft-versus CLL effect (GVCLL). Interestingly, rituximab has been shown to promote the cross-presentation of tumor-derived peptides by antigen-presenting cells, thus enhancing the formation of cytotoxic T-cell clones and a GVCLL effect. With the addition of rituximab to the conditioning regimen, rates at 4 years for current progression-free survival (CPFS) and overall survival were 44% and 48%. The investigators hypothesize that ofatumumab, having a more potent anti-CLL activity and complement-dependent cytoxicity than rituximab, could improve disease control and modulate the GVCLL effect more effectively, thus reducing the GVHD rate and subsequently improving the non-relapse mortality and progression-free survival in the long term.

På Clinical Trials har Genmab opffentliggjort et NYT studie med zalutumumab (!), som så ganske vist er blevet aflyst, inden det nåede at blive sat i værk. http://clinicaltrials.gov/ct2/show/NCT01449357?term=zalutumumab&rank=4

Studie 64, Ofatumumab fase IV ved GSK: Arzerra is designated as an orphan medicinal product in the European Union (EU) for treatment of chronic lymphocytic leukemia. The Committee for Orphan Medicinal Products (COMP) concluded that chronic lymphocytic leukemia was estimated to be affecting approximately 3.5 in 10,000 persons in the Community at the time the application was made (June 2008) and that the condition is chronically debilitating and life-threatening, in particular due to poor long-term survival in high-risk patients. Arzerra was given a conditional approval in the EU on April 19, 2010. The approved indication in the EU for the product is treatment of CLL in patients refractory to fludarabine and alemtuzumab. A specific obligation for this conditional approval was an agreement by GSK to conduct a post-marketing observational study in CLL patients receiving Arzerra. The data from this study is intended to enhance the evidence of the safety and efficacy of Arzerra as it is used in clinical practice, and once final data are available, together with results of a second specific obligation study, will support the transition from conditional to a full approval of Arzerra in the EU. The objective of this observational study is to provide additional data to confirm the safety profile and efficacy of Arzerra for CLL patients treated in clinical practice. Particular data of interest are: co-morbidities (specific chronic disease diagnoses), concomitant medications, disease (CLL) characteristics, prior treatment regimens, adverse events, reasons for discontinuation of Arzerra therapy, Arzerra response, progression free survival, and overall survival. This is an observational, non-interventional, medical record review study in CLL patients. A total of 100 patients with CLL who have previously received Arzerra, whether alive or deceased, and have either completed the full course of Arzerra therapy or discontinued treatment early will be eligible to participate in the study. Centers across Europe who are members and non members of the European Research Initiative of CLL (ERIC) and treat CLL patients will participate in the study. CLL patients newly initiating Arzerra who are still undergoing the treatment phase and patients having been treated with Arzerra in phase II or phase III clinical trials will be excluded. For patients who have completed approximately 1 year or more of follow up since Arzerra initiation, data on response to Arzerra, adverse events during treatment and subsequent to treatment, patient status, progression free survival and overall survival covering the period up to approximately one-year post-drug initiation will be collected. For patients who have not completed approximately l year of follow-up since Arzerra initiation, including those who have been lost to follow up or died prior to one year or have not yet had a full year to elapse in calendar time, similar data will be collected at the point in time at the last availa

Lene E er OGSÅ færdig

Så nåede ofatumumab op på studie 63 på clinical trials: Phase II Study of Ofatumumab in Elderly Patients With Chronic Lymphocytic Leukemia (CLL) This study is not yet open for participant recruitment. Verified on September 2011 by M.D. Anderson Cancer Center First Received on September 28, 2011. Last Updated on September 30, 2011

Og lidt mere om RA: The results from the 24-week, placebo-controlled, double-blind phase of this trial confirm the previously reported efficacy of one course of intravenous ofatumumab in active RA.11 In addition, this study provides further information on the efficacy of ofatumumab in a well-defined RA patient population with long-standing disease not controlled by standard methotrexate therapy and not previously treated with other available biological DMARD therapies. Ofatumumab, at a dose of 700 mg administered twice, added to a background stable dose of methotrexate therapy, demonstrated a significantly greater ACR20 response at week 24 (primary endpoint) compared with placebo. Significantly greater improvements were observed in key secondary endpoints such as ACR50, ACR70, change from baseline in both DAS28–CRP and DAS28–ESR, EULAR response, physical function (HAQ–DI) and fatigue (FACIT–F). ... In summary, ofatumumab is a fully human mAb binding an epitope of CD20 distinct to that recognised by rituximab. A single course of two infusions of 700 mg was efficacious and safe in biological-naive, active RA patients on background methotrexate up to 24 weeks after treatment. As expected for a fully human mAb, ofatumumab did not induce immunogenicity. http://ard.bmj.com/content/early/2011/08/22/ard.2011.151522.full

rILYd4, a Human CD59 Inhibitor Enhances Complement Dependent Cytotoxicity of Ofatumumab against Rituximab-resistant B-cell Lymphoma Cells and Chronic Lymphocytic Leukemia Published OnlineFirst September 14, 2011; doi: 10.1158/1078-0432.CCR-11-0647 http://clincancerres.aacrjournals.org/content/early/2011/09/14/1078-0432.CCR-11-0647 Citat: It is widely accepted that OFA has much more potent CDC than RTX(18, 19). Consistently, we found that OFA mediates much stronger CDC effects than RTX in all cells. The more potent CDC effect mediated by OFA compared to RTX is attributed to increased C1q binding and C3b(i) deposition on the target cells triggered. Previously, Beum et al and Pawluczkowycz et al demonstrated that OFA triggers more C1q binding and more C3b(i) deposition on these Daudi and Raji cells, leading to more MAC attack(9, 23). These results were further confirmed by us with two other lymphoma cell lines expressing high levels of CD59. The application of rILYd4 to OFA or RTXmediated CDC specifically increases C9 deposition but not C1q binding and C3b(i) deposition on the targeted cells. This result directly highlights the specificity of rILYd4 activity, the inhibition of anti-MAC activity of CD59.

takker

og at tale TA med mig svarer til at tale med en blind om farver

Det næstsidste af de rekrutterende Zalu studier er per 9. sep.2011 "active, not recruiting". http://clinicaltrials.gov/ct2/show/NCT01054625?term=zalutumumab&rank=1

Ofatumumab og bendamustine http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2011.08829.x/full Ofatumumab (2 mg/kg) and bendamustine (50 mg/kg) combination therapy resulted in a complete arrest of JVM-3 CLL growth (P < 0·001) as compared to control and monotherapy groups. Both tumour growth inhibition and tumour growth delay were significantly improved in the combination therapy group when compared to monotherapy groups.