During Play in editor (PIE), is there a shortcut to simulate ESC without stopping the game?

Technically the previous answer was correct, the location is wrong:

  1. Open DefaultInput.ini
  2. At the top, locate the section: [/Script/Engine.PlayerInput]
  3. Add the following line under all the “+DebugExecBindings” (There should be around four):

-DebugExecBindings=(Key=Escape,Command=“CloseEditorViewport”)

*Notice that the other four bindings have a “+” sign, while this “-” unbinds the original Esc key setting