Officials say the crash happened just before midnight along the 1500 block of Mountainview Drive in Haycock Township.
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Police say an SUV and a sedan crashed head-on.
The impact caused a fire, trapping four people and a dog inside the wreckage.
The two victims in the sedan, a 25-year-old man from Ottsville, PA and a 26-year-old man from Quakertown, PA, were killed, according to State Police.
A 24-year-old woman from Rockaway, NJ and a 26-year-old man from Ossining, NY were traveling in the SUV.
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State Police say the 26-year-old man is the lone survivor of the crash and was flown to Jefferson Hospital in Philadelphia.
Officials say the dog also survived and was taken to a nearby vet.
The cause of the crash remains under investigation.