Exeter’s uncapped Greg Fisilau is the secondary number eight behind first-choice Ben Earl, edging out Alex Dombrandt.
Guy Pepper has recovered from injury to take his place in the back row, while tighthead props George Kloska and Vilikesa Sela are in line for first caps.
The absence of Itoje, who recently posted pictures of himself on holiday in Mauritius to social media, opens opportunities for others in the second row.
George Martin, whose superb performance against South Africa in the 2023 Rugby World Cup semi-final will have been front of mind for head coach Steve Borthwick, only recently made his comeback from 14 months out with a string of injuries, while Gloucester’s Arthur Clark will hope to add to the solitary cap he won against the United States in July.
In the front row, Sale’s Asher Opoku-Fordjour – more usually a tighthead – will also cover loosehead prop, where Ellis Genge only recently recovered from a calf complaint and Bevan Rodd and Fin Baxter have been ruled out.
With only Immanuel Feyi-Waboso and Cadan Murley included alongside Caluori as specialist wingers, Borthwick’s selections hint at a possible return out wide for Tommy Freeman, who started at outside centre in four of England’s five Six Nations games.
Borthwick admitted the itinerary thrown up by the new Nations Championship – which has replaced the traditional single-location summer tour for northern hemisphere nations – will present a new challenge.
After taking on world champions South Africa at altitude in Johannesburg, England will play Fiji in Liverpool, before heading to the small Argentine city of Santiago del Estero to face the Pumas.
“We’ve selected a squad with a good blend of experience and emerging talent,” said Borthwick.
“The Nations Championship presents an exciting challenge for this group. We will face strong opposition in demanding environments, with extensive travel, and changes in climate all testing the squad throughout the tournament.
“I am sure by preparing well and continuing to demand the highest standards from one another every day, we will be well placed to meet the challenge of a very demanding summer schedule.”
