The collision happened just before 3 a.m. at Alameda and 8th Street, according to the Los Angeles Police Department.
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The driver of the small vehicle, a woman of unknown age, was pronounced dead at the scene.
The LAPD says speed appears to be a factor in the deadly crash. Witnesses told police the semi-truck had the green light at the time, and it appears the other driver did not attempt to brake as there were no marks on the road.
Investigators say it's unclear if the driver who died was distracted, asleep at the wheel or driving under the influence.
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The driver of the semi-truck was said to be OK.
DEVELOPING: We will add more details to this report as they become available.