The bootloader seems to refuse loading code in address ranges >= 0x80000. If the binary size of the code exceeds 496k, the loading address exceeds 0x80000 and the code will not run. The code can be loaded successfully using a JLInk adapter, so it’s not a problem of the MCU, not being able to run code from that address space.
Is that problem known, and is there a fix for it, like an updated bootloader?
Create an issue here https://github.com/sparkfun/SAMD51_Thin … is%3Aissue to alert the engineering team 
Did so, thanks. Just a personal question: do you use the user name scruss in the MicroPython forum/repository?
It seems that with the firmware supplied in PR #2 the problem is gone. The board I tested had bootloader v2.0.0-34, dated Mar 20, 2019. Link: https://github.com/sparkfun/SAMD51_Thing_Plus/pull/2