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Two of the oldest names in European rugby compete for the first time when Cammi Rugby Calvisano face Agen at Centro Sportivo San Michelle.
Calvisano will be eager to make a winning return after a three-year absence from European competition.
Much will depend upon the experience of their half-backs, former Italy pair Paul Griffen and fly-half Andrea Marcato who have remained faithful to the former Italian champions.
Agen once regularly reached the knock-out stages of Europe but not have done so since 2005, the same year they suffered their only defeat to Italian opposition, Viadana, in 12 encounters.
France great Phillipe Sella is among a knowledgable coaching staff that has helped Agen recover from a shaky start to win three of their last four games in Top 14.
Ex-Wales centre Jamie Robinson provides guile in midfield while South African fly-half Conrad Barnard already needs just one more score to hit 100 points this season.
Agen used to reach the knock-out stages of Europe on a regular basis and, while they have not done so since 2005, they took the first albeit tentative step in putting that right with a 36-31 Pool 4 victory on the road at the Peroni Stadium.
After a three-year absence from European competition Calvisano struck first when flanker Giacomo Broncoli went over for a try after just two minutes, former Azzurri scrum-half Paul Griffen converting and adding a penalty to remind Agen they had some work to do.
And they promptly got to work with a try by Leo Bastien converted by Raphael Lagarde before taking a lead they never surrendered with right wing Leka Tagotago securing the try bonus point just a minute after the break.
Scrum-half Sylvain Dupuy and No8 Uelenitoni Fona had already breached the Calvisano defence for a 31-17 half-time advantage but Calvisano showed tremendous spirit by staging a great comeback with lock Jaco Erasmus to the fore that earned them both try and losing bonus points and had Agen hanging on for victory.
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