Disable your second Monitor in the NVIDIA control panel, then disconnect it from the PC.
Reboot > Test.
If that don't helps:
Please preform a clean boot and test the Game in clean boot mode.
Make sure your virus scanner and other security software and also Afterburner and similar software is disabled in clean boot mode.
Make also sure that your GPU & CPU are not overclocked.
It works perfectly without the second Monitor, but why is that and can I fix it so that I can still use my second monitor?
I am not sure, on both accounts.
Your Samsung U28E590 runs at 1920x1080 wile his native resolution is 3840 x 2160, I assumed because it only supports 30Hz at 4K.
You can try to set a higher resolution.
You can try to disable every software that uses an overlay (Discord, Afterburner with Riva Tuner and so on) or the overlay on Steam and Origin.
You can try a different port or port type on the GPU.
You can try a different cable.
