Experienced scrum-half Ben Youngs has been left out of England's 29-man squad to face Italy in the Six Nations on Sunday.
Northampton's Alex Mitchell is included as one of the two scrum-halves along with Jack van Poortvliet.
Flanker Ben Curry, who started the 29-23 defeat by Scotland, has also been left out as has wing Anthony Watson.
Wing Henry Arundell, centre Henry Slade and flanker Jack Willis are all included.
Slade (hip) and Arundell (foot) have both recovered from injury to be available for selection.
England head coach Steve Borthwick will confirm his matchday 23 on Friday afternoon.
London Irish's Arundell, 20, made a startling impression in his brief cameos on the summer tour of Australia, and is expected to be involved against the Azzurri this weekend.
Captain Owen Farrell says the wing is a "special talent", reminiscent of one of the all-time greats of English rugby.
"He is someone who, when he gets the ball in training, I get the sense something is going to happen," Farrell told BBC Sport.
"If I'm honest there are not too many people I think that about, not too many people I would almost go to the edge of my seat when they get the ball. He is one of them.
"I am not comparing them at all, but I had that sense growing up when Jason Robinson got the ball, that he is going to do something here, and I have got that feeling when Henry has got the ball. He is a special talent."
Meanwhile, England men's record cap holder Youngs misses out on a Six Nations matchday squad for the first time since 2018.
"We have tried to select a squad that we think gives us the best chance of performing well on Sunday and winning," said defence coach Kevin Sinfield.
"We don't see this as a 15 and 23, it is very much a squad. The guys who have unfortunately gone home will be back.
"There are no mind games in any of this. We think this gives us the best chance of winning, and he [Youngs] is absolutely behind what we are trying to do.
"He is obviously disappointed, you would expect him to be, as are all the lads that are going home.
"They want to play for their country but they understand, they don't always agree, but they appreciate we are all trying to do our best here and we have to make some decisions."