This is actually a system error on Apples side that was introduced with the 16.4 iPadOS update.
I've been trying for the past month to solve this issue together with the developer via hundreds of emails and differnt approaches, but unfortunately there is just no way to fix this. It happens only on bigger documents.
In the recent Beta (that propably will soon be on AppStore) there will be error messages that pop up whenever this occurs, so you now at least to immediately copy layers to a different document and to restart the app, to avoid losing progress. Also changing the default saving location from "iCloud Drive" to "On my iPad" in ipad Settings > Artstudio Pro and to save new Files in Files > On my iPad > Artstudio Pro , can minimize how often it happens, and how much work you lose. It will also get rid of lags, incase you experience those as well (But only new files will be saved there, for existing files you need to move them manually). You can still upload the files to iCloud manually after you finished painting. Saving manually instead of autosave won't make a difference unfortunately.
The same kind of issue is also occurring in the Pages and Numbers app from apple. The only thing we can do is trying to make Apple aware of this bug... The ASP developer has opened a thread on Apple discussion, you can reply to and you could use the Apple feedback assistant to report this. https://discussions.apple.com/thread/254870123
I know this is very annoying, I've also lost hours of work due to this becaue my documents are alway pretty big. But for now all we can do is to hope for Apple to fix it soon...