Optimistically, I went with galactic collision. Realistically, I'd lean towards major impact, but it'd have to be a doozy. Homo sapiens survived for tens of thousands of years without modern civilization; related species survived for hundreds of thousands of years. If you get a 99% human die-off event, the species would still be just fine afterwards.
The big question is if we're going to plateau around our current level of science or if it'll jump forward, probably through genetics, and then plateau. If the former, we'll probably regress at some point (pandemic, impact) and then rediscover; if the latter, all bets are off. Eventually we'll try engineering aquatic humans, space humans, etc, etc. Technologically I suspect our theory will outstrip our practice; we might find a theory that allows wormhole traffic, but requires the mass of Jupiter to create.
Then again...I dunno. I am pretty pleased to be alive at this point in time. It's interesting.