It happened around 9:30 p.m. Thursday on Cobbs Creek Parkway near Upland Street.
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Police said a driver lost control of a Jeep Cherokee and struck a tree. The vehicle then went down an embankment and landed in the creek.
Authorities said there were five people inside the vehicle.
First responders arrived to the scene and pulled victims from the vehicle.
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All five were taken Penn Presbyterian Medical Center.
Two people died from injuries sustained in the crash. The three other victims are listed in serious, but stable condition.
Action News has learned one of the people killed in the crash was a 17-year-old boy. The other people in the car were all under 18.
Dhanya Andrews, 19, said his friends were involved in the crash.
Andrews said he grew up with Marquan Payne, who was driving the car.
"I grew up with Marquan like sandbox like always been my friend. That's the one I could count on," he said.
Andrews said he is still working to find out who else was in the car, and that was supposed to be in the Jeep with his friends.
Police are investigating.