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http://bindingofisaacrebirth.gamepedia.com/Challenges
lists the requirement as:
it's for this reason that i assume you maybe have to beat mega satan once too as you have to do it in the challange. for me i had allready beat it before i get the knife so i can't be sure.
looks like since you need the key peices you get from bombing the angels in the angel rooms, which triggers a mini-boss fight
I do know that beating Mega Stan before the challenge isn't a requirement. I've never beaten him and I unlocked it.
yeah you need the negative as you have to go by sheol (there is no cathedral in this run) to go to the mega satan of this challenge.
http://bindingofisaacrebirth.gamepedia.com/Challenges