After fiddling with tools a bit (it looks like neither AS7 nor MPLABX 5.1 is quite up to using a PICKit4 with SAMC21), I have the board responding, have uploaded an empty C program, and can single-step through the C runtime startup code.

(Using (upgraded) MPLABX 5.25 and the PICKit4, on MacOS...)

So that's pretty significant!  Next up, Blink!