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Officials said the incident happened before 1:15 p.m. Thursday afternoon on NC 72, 5 miles southeast of Pembroke, just west of Lumberton.
The 2007 International tractor trailer carrying chemicals ran off the road, struck a highway sign before over-correcting back onto the roadway, and overturning.
The 2004 Mitsubishi steered off the road to the right to avoid impact with the truck, but it ended up colliding with the car, causing them to catch on fire.
The driver of the truck - 63-year-old Otis Enoch Jr. of Whitsett, NC - was trapped in the vehicle and pronounced dead at the scene.
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Driver of the car - 57-year-old Wendell McRae of Lumberton - and the front seat passenger - 29-year-old Niasia Oliver - were both airlifted to McLeod Hospital in Florence.
Their 1-year-old daughter, Windshae McRae, was trapped in the back seat and pronounced dead at the scene.
Authorities said it was unclear why Enoch ran off the roadway, but neither speed nor alcohol are considered factors.
An investigation is ongoing.