Yarchoan M, Cope L, Ruggieri AN, et al. - In biliary tract cancer (BTC) cases, a prolonged progression-free survival (PFS) is conferred by the combination of atezolizumab plus cobimetinib vs atezolizumab monotherapy, but in both arms, low response rate was observed which highlights the immune-resistant nature of BTCs.

• In this open-label phase II study, 77 patients with BTC were randomized to atezolizumab (anti–programmed death ligand 1) as monotherapy or in combination with cobimetinib (mitogen/extracellular signal–regulated kinase inhibitor).

• Primary endpoint was achieved, with a median PFS of 3.65 months in the combination arm vs 1.87 months in the monotherapy arm (HR 0.58).

• A partial response was seen in one patient in the combination arm (3.3%) and 1 patient in the monotherapy arm (2.8%).

• More rash, gastrointestinal events, CPK elevations, and thrombocytopenia occurred with combination therapy.

• In exploratory analysis of tumor biopsies, combination therapy was associated with enhanced expression of antigen processing and presentation genes and an increase in CD8/FoxP3 ratios.

• Greater clinical benefit from the combination was evident in patients with higher baseline or lower fold changes in expression of certain inhibitory ligands (LAG3, BTLA, VISTA) on circulating T cells.