The new game will take place some considerable time after the events of the Mass Effect Trilogy. You will play the commander of a starship exploring the Andromeda Galaxy, having made the dangerous intergalactic journey from the Milky Way. The game will apparently feature a mixture of established, "classic" races from the original games and some new species you encounter in the new location. The game's setting will allow BioWare to minimise references to the original trilogy.
No word yet on the storyline, but the game's structure will see your ship exploring new worlds both from orbit and using the Mako ground vehicle, which plays a bigger role this time around and can be upgraded. The game is set for release in late 2016.