Large signal S parameters are when you can non longer assume your system is linear. There is no one Large Signal S parameter, it is a function of how saturated your components are.
Sometimes a system considered to be in large signal, may have only one active component that is non linear, all the rest of the componets may be linear, especially if they are passive. The linear components will have no S21 change although the system is considerd in large signal.
Typically, S21 large Sig < S21 small sig.