A 15-storey office development at the northern end of Blackfriars Road was given the go-ahead by Southwark's planning committee this week.
The development by Great Portland Estates will replace the KMPG offices, Cafe Arlington and the Elspeth Kyle Gallery on the eastern side of Blackfriars Road between Southwark Street and Burrell Street.
Both buildings are due to have a restaurant/cafe or retail unit at ground-level.
The current tallest building on the site is 5 storeys.
Planning officer Adrian Dennis described the development, known as 240 Blackfriars Road, as "a well-designed scheme that relates well to this location".
The building will be "an urban marker, a key project as you come into the borough", Simon Allford of architects Allford Hall Monaghan Morris told councillors.
Allford highlighted to the committee the "play of contrasts" between the taller office building and the much smaller residential building and the "generous pavement" afforded by the cut-away at the bottom of the buildings.
Great Portland Estates bought the Cafe Arlington and Elspeth Kyle Gallery premises from Novas Group last year for £3 million. It is understood that the cafe and gallery are able to remain in the building rent-free until development commences.
Last year Derwent Valley Holdings won permission for a 10-storey building on the site of Wedge House, currently occupied by the Benefits Agency.
Another current planning application for Blackfriars Road would see the demolition of the small building on the corner with Scoresby Street and its replacement with an extension to the Lloyds TSB offices. The whole building would also gain an extra storey.
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