Troopers were called to the crash site on Lancaster Pike, near Hercules Road, just after 4 p.m. after a passing motorist noticed a vehicle off the roadway.
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When troopers arrived, they found a 42-year-old man from Oxford, Pennsylvania, dead at the scene.
Lancaster Pike was then closed down for approximately four hours while the crash was investigated.
The investigation revealed that between November 25 and December 6, the driver of a black Mitsubishi Outlander was traveling westbound on Lancaster Pike when, for unknown reasons, the vehicle crossed into the eastbound lane and off the south edge of the road. The vehicle eventually crashed into a guardrail but continued though some vegetation before hitting two trees.
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During the crash, investigators say the driver was ejected from the vehicle before it came to a rest in a creek just south of the roadway.
The driver's name has not yet been released, pending notification to his family.
The investigation is ongoing.