The crash happened on DeSoto Avenue near Plummer Street in the late afternoon.
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Police say a 2011 Infiniti M37 was speeding southbound on DeSoto when it smashed into a 2004 Toyota Avalon that was turning left from DeSoto to Plummer.
Witnesses told police a gray sedan was driving southbound on DeSoto along with the Infiniti when the crash happened.
Inside the Toyota, a 72-year-old male driver and his 73-year-old female passenger, died at the scene. Riding in the backseat of the car was a 9-year-old girl who was seriously injured and transported to a local hospital in critical condition.
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Their names have not been released pending notification of next of kin.
The driver of the Infiniti was a 26-year-old man from Granada Hills who was also severely injured and was transported to a local hospital.
The cause of the crash remains under investigation.