The crash involving the car-hauling big rig was reported shortly after 3 a.m. on the eastbound side of the freeway, near Kramer Boulevard, according to the California Highway Patrol.
The identity of the driver, who died at the scene, was not immediately released.
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Debris flew onto the westbound side of the freeway, causing at least five other vehicles to sustain damage including flat tires, the CHP said.
A SigAlert was issued and all eastbound lanes were shut down for about two hours as crews cleared the scene.
The cause of the collision is under investigation.