The MEK inhibitor cobimetinib added to atezolizumab was investigated in a phase II trial and showed a progression-free survival of 3.6 months in the combination arm versus 1.9 months in the monotherapy arm.243 Another phase II trial investigating bintrafusp alfa, a bifunctional fusion protein did not meet its primary endpoint with ORR of 10.7% targeting PD-L1 and TGF-β in patients with pretreated CCA.244 Combination of chemotherapy with immunotherapy has become standard of care in the first-line therapy of CCA. Here, TGFB1 is linked to cholangiocarcinoma.