England hooker Dylan Hartley is set to miss out on the World Cup after struggling with a knee problem.
Regular captain Hartley led England to back-to-back Six Nations titles in 2016 and 2017 under head coach Eddie Jones, but hasn't played since December.
Jones is also set to shun hundreds of caps worth of experience when he names his first training squad on Thursday.
Scrum-half Danny Care and flanker Chris Robshaw are understood to be among the high-profile omissions.
Thursday's 29-man party will only include players not involved in the Premiership semi-finals, with Harlequins' uncapped forward Alex Dombrandt in line to be named after a strong performance against the Barbarians earlier this month.
With all English-based players given a mandatory rest period of five weeks, those from beaten semi-finalists Gloucester and Northampton will join the camp next week.
Jones then names his final training party, including players from finalists Exeter and Saracens, on 4 July.
'Hartley not in right condition'
Hartley, 33, was an ever-present part of Jones' regime before he missed the tour of South Africa last summer because of concussion.
He has struggled to nail down a regular place since, and has not featured for either club or country in 2019 because of a recurring knee problem.
Although as a Northampton player he was not due to join the camp until the end of the month, it is understood he is not in a fit enough condition to be involved.
Sources close to Hartley say he will continue to rehabilitate his injury in the hope to be fit and available in August, but in reality the odds are now firmly against him making the tournament in Japan.
'Omissions a gamble'
Even though they have fallen out of favour of late, Care, 32, and 33-year-old Robshaw's exclusions come as a major surprise and represent a gamble from Jones.
Care, England's second-most capped scrum-half with 84 appearances, was a regular part of the squad before being left out of the tour of South Africa in summer 2018.
Despite playing against both the Springboks and New Zealand that autumn, as well as scoring a try against Japan, he was dropped for the match with Australia and did not feature in the last Six Nations.
Gloucester's Willi Heinz, Saracens' Ben Spencer, Wasps' Dan Robson and regular starter Ben Youngs are set to be the scrum-halves called into camp.
Along with Care, another experienced operator in 36-year-old Richard Wigglesworth is also thought to have been overlooked.
Flanker Robshaw was also a squad mainstay before having knee surgery in October and missing the autumn internationals.
The former England skipper has not played for his country since, with Mark Wilson and Brad Shields commandeering the blind-side flanker position.
Meanwhile, Northampton's uncapped back-rower Lewis Ludlam, 23, is understood to have shot into late contention.
Marler considering coming out of retirement
Meanwhile, prop Joe Marler is considering coming out of retirement for the showpiece in Japan.
The 28-year-old, who has 59 caps, announced the end of his international career in September in order to spend more time with his family.
But he is thought to be weighing up a return, and is again a part of England's Elite Playing Squad - which is not made public.
If he decides to make a comeback, Marler would not be named in the training squad until the start of July given he played for the Barbarians against an England XV on 2 June.
Source: BBC Rugby Union News