Nibali, who did not compete in this year's Tour, waited his turn to attack while Alberto Contador, Romain Bardet (AG2R) and Lopez formed a group ahead of Froome's bunch.
Astana climber Lopez danced past Britain's Adam Yates (Orica-Scott) on the final climb of the short but fiendishly sharp stage in the mythical Sierra Nevada mountains to double his winning tally in the 72nd edition of the race. "With regards to my performance, I am not back to my best form yet following the crash and I am hoping to have a good day during the last week and win a stage".
At the time of going to press, Chris Froome is still leading the pack after he finished second on the 11 stage, 187.5km route from Lorca to Observatorio de Calar Alto.
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An exhausted Yates, who is yet to win a stage at a Grand Tour, was caught in the final 4km, nearly coming to a halt as Lopez raced past him.
A late surge by Froome over the final meters of the punishing ride and a final special-category ascent allowed him to increase the gap over Vincenzo Nibali from 55 seconds to 1:01.
The fight to get into the break at the Vuelta has normally been one that's taken hours and well over 50 kilometres, but the escape today went early and quite simply.
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Lopez dominated the last climb of an action-packed day to claim a solo victory ahead of Ilnur Zakarin (Katusha-Alpecin) and Wilco Kelderman (Sunweb).
Miguel Angel Lopez was 27 seconds back in second. "But we made a decision to go for it", Trentin told reporters after edging out 14 other riders in the uphill sprint finish to cross the line first in Tomares.
I can't thank my team-mates enough. I think it was the right decision, we've kept the energy for the stage tomorrow [Sunday], " responded Froome. "It didn't work out today but I am sure it will in the future".
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We knew Majka was stronger than most of us in this kind of stage finish and his teammates did a great job in supporting him throughout.