Defeat Megaera and the Titan Hecatonchires
Story related. Cannot be missed.
Will unlock in Chapter 4: The Hecatonchires.

Eventually you will reach the head of the Titan Hecatonchires who is bound with a platform in his mouth. Shortly thereafter Mageara will appear and infect the head which then sprouts prongs from his mouth, similar to the ones on Magearas back. The two prongs closest to the bottom of the platform are infected and vulnerable to attack. Fend off the smaller attackers is a good way to do damage to them all, push them back, while minimizing your damage intake during the many violent camera shiftswhile destroying each prong as quickly as possible.

Once you successfully destroy one you will be launched to another bridge where you will fight another Hand of Aegaeon. However this time you will be able to mount it after it is weakened, similar to the Cyclops, and have it attack the head. Once you have done enough damage the Titan will bite down on the Hand and the trophy will unlock.