Harlequins centre Joe Marchant will start England's final warm-up match against Italy on Friday despite not being part of the World Cup squad.
Marchant is alongside Piers Francis in the midfield in what is described as a "mix and match selection strategy".
Ruaridh McConnochie will finally make his debut on the wing and joins Jonny May and Anthony Watson in the back three.
Billy Vunipola makes his fourth start of the campaign at number eight.
"We have gone with a mix and match selection policy to develop our adaptability and the team's ability to cope with any situation," explained head coach Eddie Jones.
Friday's match in Newcastle will be the first England Test match to be staged at St James' Park.
Jones' side then fly out to Japan on Sunday before their tournament opener against Tonga on 22 September.
"We are playing at an iconic football ground and we know the area is an important one for rugby in the northern part of England," Jones added.
"We are looking forward to seeing and playing in front of the fans."
Marchant made his England debut as a replacement against Wales last month before also coming on against Ireland a fortnight ago.
His inclusion raises questions over the fitness of Jonathan Joseph, after the Bath man pulled out of the Ireland game with unspecified muscle soreness.
Fellow centre Henry Slade is also missing, and has not played a minute of rugby since picking up a knee injury in camp last month.
Meanwhile Vunipola's inclusion in the back-row for the fourth consecutive match appears a gamble by Jones.
However assistant coach Neal Hatley said on Thursday the England management had no concerns about Vunipola's workload.
"One of the key things with Billy is to keep him playing," Hatley said.
Captain Owen Farrell starts at fly-half for the first time in the warm-up schedule, while Anthony Watson plays at full-back for the first time since March 2018.
"We have had a solid training week in Treviso with hot conditions so we are looking forward to testing ourselves against Italy on Friday night," Jones added.
"Then we hop on the plane and are ready to go to Japan."
England: Watson; McConnochie, Marchant, Francis, May; Farrell (c), Youngs; Marler, George, Cole, Launchbury, Lawes, Curry, Wilson, B Vunipola.
Replacements: Cowan-Dickie, Genge, Sinckler, Ewels, Kvesic, Heinz, Ford, Cokanasiga.