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He was born into a noble family, as the son of the count palatine Cesare Calcagnini, marquess of Fusignano and a relation of cardinal Carlo Leopoldo Calcagnini. He studied at the Collegio dei Nobili di San Carlo at Modena and then at the Sapienza in Rome – at the latter, on 15 May 1747, he gained a doctorate in theology and in utroque iure.
He entered the papal court as private chamberlain to the pope in 1746.