Labbett and Gamble co-founded Saint with Adam Graham in May 2007 and have been responsible for managing the agency's strategy and group positioning.
Labbett and Gamble's departure confirms a tumultuous end to the year at RKCR/Y&R. Chief executive Richard Exon and executive creative director Damon Collins announced they would be leaving in early 2012 less than three months ago.
Graham left Saint@RKCR/Y&R in September to become chief executive of Weapon 7. RKCR/Y&R clients include Marks & Spencer, Warburtons, Virgin Atlantic and Lloyds TSB.
Alison Hoad, joint chief executive of RKCR/Y&R, said: "We are sad to see Simon and Dave leave after many successful years at the agency but wish them the best of luck with their future projects."
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This article was first published on campaignlive.co.uk