Would you consider a comedian to be able to fill the role of femme fatale?
Usually when a femme fatale appears in comedy, it seems to me that she’s there to serve as a joke against the archetype rather than as a true femme fatale.
Just look at Barbara Stanwyck. Her femmes brought as much humor as sultry to the role. And River Song’s propensity for clever one-liners doesn’t detract from her femme-ness at all. I will say, though, that most often, the humor is added value to a dramatic plot, rather than a comedy-based work to begin with.
I'd go so far to say that the best of the femme fatales used humor to hold their own against the male leads they faced and flabbergasted.