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HuMax-CD20 Clinical Trial Results

Date: November 16, 2007

“Ofatumumab” is not a name that rolls off of the tongue too easily. But if you are a CLL patient, you had better remember this monoclonal antibody is none other than HuMax-CD20. Chances are excellent that you will be using this drug sooner or later. I for one will be rooting for the day when this important monoclonal is an approved drug and commercially available for treating CLL.

One of the first clinical trials using HuMax-CD20 in CLL patients was initiated a couple of years ago. Patients recruited for the trial were a refractory cohort, people who had flunked both fludarabine and Campath. As we have seen in a recent article on the subject of refractory CLL, people who have failed fludarabine and Campath have precious few options and face a grim prognosis, no matter what. Here is the link to our article on the subject: Refractory CLL – but please be warned this is not easy reading for the faint of heart, and please don’t shoot the messenger.

So, when Genmab took on the challenge of seeing if their fully human anti-CD20 monoclonal antibody can possibly work with this refractory and hard-to-treat patient cohort, I was both pleased and skeptical. After all, everything we have seen up to now suggested a similar anti-CD20 monoclonal antibody, Rituxan, as single agent did next to zip, nothing, nada for this type of CLL patient. What were the chances this Johnny-come-lately Rituxan look-alike would be able to do what mighty Rituxan could not?

Well, the results of this pivotal trial have just been published in prestigious the Blood journal. The abstract is below and if you want to read the full text of the article with lots of juicy details that are not in the abstract, write to us and we will see what we can do to help you get hold of this hot-off-the-presses article.

Bottom line, an encouraging 50% of the patients responded to HuMax-CD20. That is definitely a half-full glass, as I see things now. In my personal opinion (and we surfaced this issue in a prior article on our website), the prudent patient will seek to be on prophylactic anti-bacterial and anti-fungal medications while undergoing HuMax-CD20 therapy. Frankly, there are precious few CLL therapies where the belt-and-suspenders approach to protecting the patient from opportunistic infections is not a good idea. GPs prescribe anti-bacterial medications at the drop of a hat in general practice, and folks get daily Valtrex / Famvir to prevent cold sores that interfere with peoples’ social life, for crying out loud! What is the problem protecting infinitely more immune suppressed and at-risk CLL patients as they go through therapy? Search me if I understand this logic…

Notice this trial looked at using weekly infusions of HuMax-CD20 as a single agent for 4 weeks. Considering these patients were pretty tough cases, some of them had remarkably long-lived remissions. Most of the adverse reactions occurred during the first infusion (“urticaria” or hives was a frequent one, as we documented in a prior “Harvey” article). Majority of the patients received 500 mg on the first infusion, and 2,000 mg on the three subsequent infusions. The maximum tolerated dose was not reached. I wonder if the single case of fatal pneumonia would have happened if this patient and the rest of the cohort had been on anti-bacterial and anti-viral medications for the duration of the trial. Live and learn, I suppose.

This trial is the beginning of the story for HuMax-CD20. Like Rituxan, I am pretty sure the major value of this new antibody is going to be in its synergy with various other CLL drugs, along the lines of HuMax + FC (similar to RFC) and the like. Now we need to keep our fingers crossed that our beloved FDA will approve its use in CLL with all due diligence.

HuMax Risks and Rewards
HuMax-CD20: A Smarter Monoclonal
"Harvey" Does HuMax-CD20
HuMax-CD20: Interim Results
HFC Clinical Trial Recruiting Chemo Naive Patients

Be well,

Chaya
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Abstract:

Blood. 2007 Nov 14

Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia. A phase I-II study.

Coiffier B, Lepretre S, Moller Pedersen L, Gadeberg O, Fredriksen H, van Oers MH, Wooldridge J, Kloczko J, Holowiecki J, Hellmann A, Walewski J, Flensburg M, Petersen J, Robak T.

Departement d'Hematologie, Centre Hospitalier Lyon Sud, Pierre-Benite, France.

Safety and efficacy of the fully human anti-CD20 monoclonal antibody, ofatumumab, was analyzed in an open label, multicenter, dose-escalating study including 33 patients with relapsed or refractory chronic lymphocytic leukemia. Three cohorts of 3 (A), 3 (B) and 27 (C) patients received 4, once weekly, infusions of ofatumumab at the following doses: A 1x100 mg + 3x500 mg; B 1x300 mg + 3x1000 mg; C 1x500 mg + 3x2000 mg. 67% of the patients were Binet stage B and median number of previous treatments was 3. The maximum tolerated dose was not reached. The majority of related adverse events occurred at first infusion and the number of adverse events decreased at each subsequent infusion. 17 of 33 patients (51%) experienced infections, 88% of them of grade 1-2. One event of interstitial pneumonia was fatal; all other cases resolved within one month. The response rate of cohort C was 50% (13/26), one patient having a nodular partial remission and 12 patients partial remission. In conclusion, ofatumumab was found to be well tolerated in patients with CLL in doses up to 2000 mg. Preliminary data on safety and objective response are encouraging and supports further studies on the role of ofatumumab in CLL patients. This trial was registered at www.clinicaltrials.gov as NCT00093314.

PMID: 18003886
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