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Two men have been arrested on suspicion of causing death by dangerous driving after two lorries and a minibus collide.
The vehicles collided while travelling on the southbound carriageway between junctions 15 and 14.
Four people have been taken to hospital with injuries.
All those killed and injured were travelling in the minibus.
Ollie Miller, who drove past the scene on Saturday morning, told Sky News: "It looked horrible, the two lorries were smashed badly and I could see a car or minibus underneath one of the lorries. It was totally destroyed, the car/minibus was basically flat."
It is believed the minibus had travelled from the Nottingham area.
Chief Inspector Henry Parsons said: "Emergency services are currently on the scene responding to this collision and road closures are in place.
"We would ask all motorists to please avoid the area, use alternative routes and await further updates before attempting to travel on this route. We appreciate motorists' patience while we deal with this serious incident.
"I would appeal to anyone who witnessed the collision and has not yet spoken to officers to please contact us. Anyone who has any information which could assist the investigation should call the 24-hour Thames Valley Police enquiry centre on 101."