It's finally time for the final boss battle! Let's smash the Lizard's face in!
Amazing Spider-Man Video Walkthrough | How to beat the Lizard
Start by trading your standard punches with the Lizard, making sure to dodge his attacks. If you use web escape, he'll come after you, though it seems preferrable to letting him slam you with his tail swipe. Whenever the Lizard is close to a wall, use Web Rush to pin him to it, then quickly run over to the smashed up Spider-Slayer robot and start digging through the rubble to find the antidote. Keep subduing the Lizard until you find the serum, then chase him down into the sewers to finish this battle.
In the second half of the fight, the Lizard will be jumping around on the sewer platforms. Use web shot to slow him down, then web rush in to begin your attack. There's a bit of a rock paper scissors feel to the fight here, only attack when he looks open, and make sure to dodge when he gets close. The first time you try to inject him with the antidote, he'll likely knock you down the chasm. Use your web slinging to get back on the pedestals and again use web shot to slow him down and go in for the kill. Hammer on the action button to jam that antidote into Connor's neck and… congratulations! You've just beaten the Amazing Spider-Man!