Humanized anti-cd70 antibody: phase I study for CLL / MCL

[Guest guest]

Greetings,

When considering dose-finding studies we've learned from experence that it's

important to ask if all patients will receive increasing doses of the study

drug. That is, if the agent appears safe at the starting dose in , will

get the increased dose next time, not just the next group of participants?

I can't tell from the protocol description how this will be handled, and I don't

know if this would be the safest way to go about introducing a new drug.

In general, Phase I studies have a low probability of providing benefit,

particularly if many of the participants will get very low doses. Benefit

cannot be assumed (at any dose) in early phase studies so these should only be

considered, I think, for people who are not benefiting from other available

options.

Anyhow, what's interesting to me (a layperson) about this target is that it

binds to activated cells, including immune cells that may be aiding and abetting

the malignant behavior in the microenvironment. Cellular expression of cd70:

Activated T and B cells, and macrophages ... TNF family relationship.

~ Karl

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Phase 1,Open Label,Dose-Escalation,Multidose Study in Relapsed/Refractory

Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma

http://clinicaltrials.gov/ct2/show/NCT00730652

" MDX-1411 is a fully human monoclonal antibody that targets the CD70 receptor,

which is a member of the tumor necrosis factor (TNF) family. CD70 is expressed

in a number of cancers, including ccRCC primary tumors and metastatic lesions.

Preclinical in vitro studies showed that MDX-1411 binds to CD70 positive cells

and induces antibody-dependent cellular cytotoxicity (ADCC), an important

mechanism of action of therapeutic antibodies that induces the destruction of

targeted cells by the immune system. Preclinical in vivo studies conducted in

ccRCC xenograft models demonstrated anti-tumor activity. "