Di2 compatibilty

The official way to work this out is to figure out the drivetrain/derailleur capacity.

Here's a page from Wiggle that explains it: https://guides.wiggle.co.uk/rear-derailleurs-buying-guide

So, to work out the relevant capacities:

Current setup: (50-34) + (34-11) = 39T

Proposed setup: (50-34) + (40-11) = 52T

Now, from what I can see, the RX800 GS has a rated capacity of 39T which I got from here: https://bike.shimano.com/en-EU/product/component/ultegra-rx/RD-RX800-GS.html

So, that means that the rear derailleur cage is too short to handle the difference. In practise, it can partially work, but will have trouble with some of the gear combinations.

To get around this, you could try changing the front chainrings to smaller numbers of teeth so that the gearing is lowered without needing to change the rear cassette, though the top speed will also be reduced.

Alternatively, you could try finding a long cage version of the rear derailleur, though from a quick search, I couldn't find any. You could try swapping the cage from a different Shimano derailleur (i.e. non-Di2), but that's getting into hack territory.

Actually, I just found the following page on Road.cc that explains drivetrains: https://road.cc/content/feature/213519-struggling-hills-if-you-need-lower-gears-make-climbing-easier-heres-how-get

There, Mat suggests that he did get a 11-40 rear cassette working with a GS derailleur, so it might be worth a try.