Understand that dropping support is in some sense a difficult decision. Perhaps eventually such will be needed; that decision is up to you of course. Current calibre I believe requires 10.14, though you may wish to maintain support for older for longer.
As it is this time of the year, plus other things are going on, it could mid-next week when I get the new machine, the following week, or a bit after. I’ll likely soon afterwards try a build, and at least report how the current runs under Rosetta 2. As you say, it should be fine.
Depending on difficulty of patches and hunting down issues, maybe it won’t be so bad, or maybe I’ll get stuck here or there and then put off the next step for a bit. I will really try to reach completion eventually.
There is mention of a qtwebengine patch for
5.15.3. Perhaps such and the other patches can be backported though you’d know more about that. There is the question of whether the Qt maintainers will backport 6.x work to 5.15. According to that thread, it’s undecided though I haven’t looked elsewhere to understand the current state of things.
Overall, I have a great interest in finding out of a native build is possible – I very possibly will attempt such with calibre too –, and am happy to document it if successful so you can decide how you wish to proceed.