Uncapped Iyogun replaces Beno Obano and Cunningham-South comes in for Cadan Murley, both of whom were hurt in Saturday’s 45-21 loss to South Africa in Johannesburg.
England added wing Tom Roebuck to their squad on Monday after fullback George Furbank was ruled out with appendicitis.
They will travel to Argentina for their third fixture in this year’s inaugural Nations Championship, a test on July 18.