[xp38]

The line of succession has never gone past the VP in usage. Always a first time but it would require very unusual circumstances.

[NautiNurse]

Very unusual circumstances include a demented POTATUS, followed by

Heels Up Harris,

Vacant Speaker of the House,

the illustrious Patty Murray (D-WA).

Yikes!

[Verginius Rufus]

After Spiro Agnew resigned, Elizabeth Holtzclaw wanted to prevent the confirmation of Gerald Ford to be the new Vice President so that a Democrat, Carl Albert, the Speaker of the House, would be in line to take over.

It isn't clear if a person who succeeded if both the Presidency and Vice Presidency would be "President" or just "Acting President."