Most likely yes. The cable clamp is listed for certain combinations of cables. You're probably not going to find one rated for more than 2 cables. There is a very specific method where you can have a large pipe stub coming out of the panel top. But it is very fussy and specific for how you do it and I can't find that section in the code book. It just seems easier to run 2 cables through each knockout using a clamp rated to hold 2 cables of that size.
If this is residential and the cables are NM, it gets more confusing as older NM cable is fatter than newer NM-B. The clamps and staples don't always differentiate which cable type they are talking about.