Consequently, to cope with this mechanism of primary resistance, a combination of an inhibitor of PI3K (copanlisib) with nivolumab has been proposed in a phase I/II study in pretreated patients, with a second phase in which the primary endpoint is a 6-month ORR in MSS CRC patients, either PIK3CA wild-type or PIK3CAm [130,131]. Here, PIK3CA is linked to colorectal carcinoma.