The crash happened around 8:30 pm near North and Temperance.
The California Highway Patrol says a semi-truck ran a stop sign before a pick-up truck hit the side of the trailer.
The driver of the semi did not stop after the crash.
Investigators say a 20-year old man and his younger teenage brother were taken to the hospital with minor to moderate injuries.
Authorities are now searching for a red big rig with a white trailer.
They believe it has damage on the right side of the trailer.
Stay with Action News for the latest updates on this developing story.