The two Britons had been due to meet at London's O2 Arena on August 12th in a rematch of their 2015 bout, won by Joshua, at the same venue.
Matchroom said in a statement that the Voluntary Anti-Doping Association (VADA) had informed them and the sanctioning bodies that Whyte "returned adverse analytical findings as part of a random anti-doping protocol."
"In light of this news, the fight will be cancelled, and a full investigation will be conducted."
Whyte lost a title challenge to WBC world champion Tyson Fury in April 2022. Joshua lost his WBA, WBO, IBF and IBO belts to Ukraine's Oleksandr Usyk in September 2021.
The outcome of the Joshua v Whyte fight could have put either fighter in the frame for a lucrative clash with former WBC champion Deontay Wilder.
"I can confirm without a shadow of a doubt that I have not taken the reported substance, in this camp or at any point in my life," said Whyte.
"This is not the first time that I have been reported as having an adverse finding for a substance which I have not taken, and as I did last time I will again prove that I am completely innocent."
