In 1526, Pope Clement VII concluded the treaty forming the League of Cognac, allying the Papal States with the Kingdom of France, the Republic of Venice, and the House of Sforza against Charles V, Holy Roman Emperor. On May 22, 1526, Cardinal Ciocchi del Monte was one of the leading commissioners responsible for preparing the Papal States for the War of the League of Cognac. His efforts, however, were totally inadequate to prevent the Sack of Rome (1527). He was one of the small number of cardinals who remained loyal to the pope, seeking refuge with him in the Castel Sant'Angelo. On June 5, 1527, he was one of the seven cardinals who signed the capitulation to the imperial forces and his nephew, Giovanni Maria Ciocchi del Monte (the future Pope Julius III) was taken hostage by imperial forces.