England head coach Eddie Jones has omitted five senior players including George Ford and the Vunipola brothers from his squad.
Billy and Mako Vunipola are missing from the 45-man training group that will meet in south-west London for a three-day camp on Sunday, plus their Saracens teammates Jamie George and Elliot Daly.
Completing the list of purged veteran Test stars who have been mainstays of the Jones era is Ford, the Leicester Tigers fly-half who shined for Leicester in their season opening victory over Exeter Chiefs at the weekend.
Like Billy Vunipola, Ford was given the summer off rather than play in the July Tests against the United States and Canada.
Mako Vunipola, Daly and George were involved in the recent British and Irish Lions tour to South Africa yet cannot win places in the squad that will begin preparations for matches against Tonga, Australia and South Africa.
Other seasoned campaigners Ben Youngs, Owen Farrell, Courtney Lawes, Joe Marler, Jonny May and Anthony Watson are all included, while there are some new faces.
In all, Jones has named eight uncapped players in Mark Atkinson, Jack Kenningham, Louis Lynagh, Gabriel Oghre, Raffi Quirke, Sam Riley, Bevan Rodd and Ollie Sleightholme to train at Teddington.
Nine of the 16 new caps awarded against the USA and Canada are also present in Jamie Blamire, Trevor Davison, Alex Dombrandt, Joe Heyes, Lewis Ludlow, Adam Radwan, Harry Randall, Marcus Smith and Freddie Steward.
England’s 45-man training squad
Forwards: Jamie Blamire (Newcastle), Callum Chick (Newcastle), Luke Cowan-Dickie (Exeter), Tom Curry (Sale), Trevor Davison (Newcastle), Alex Dombrandt (Harlequins), Charlie Ewels (Bath), Ellis Genge (Leicester), Joe Heyes (Leicester), Jonny Hill (Exeter), Ted Hill (Worcester), Maro Itoje (Saracens), Jack Kenningham (Harlequins), Courtney Lawes (Northampton), Lewis Ludlam (Northampton), Lewis Ludlow (Gloucester), Joe Marler (Harlequins), George Martin (Leicester), Beno Obano (Bath), Gabriel Oghre (Wasps), Sam Riley (Harlequins), Bevan Rodd (Sale), Sam Simmonds (Exeter), Kyle Sinckler (Bristol), Will Stuart (Bath), Sam Underhill (Bath).
Backs: Mark Atkinson (Gloucester), Owen Farrell (Saracens), George Furbank (Northampton), Ollie Lawrence (Worcester), Louis Lynagh (Harlequins), Max Malins (Saracens), Joe Marchant (Harlequins), Jonny May (Gloucester), Raffi Quirke (Sale), Adam Radwan (Newcastle), Harry Randall (Bristol), Dan Robson (Wasps), Henry Slade (Exeter), Ollie Sleightholme (Northampton), Marcus Smith (Harlequins), Freddie Steward (Leicester), Manu Tuilagi (Sale), Anthony Watson (Bath), Ben Youngs (Leicester).