CTLA4 and non-small cell lung carcinoma: In the phase III MYSTIC study, durvalumab plus tremelimumab did not significantly improve OS or PFS compared with chemotherapy in metastatic NSCLC.456 For advanced, pretreated, immune-checkpoint inhibitor-naive LSCC, the addition of ipilimumab to nivolumab did not improve outcomes.457 These results demonstrate the need for a better mechanistic understanding of the crosstalk among anti-PD-1, anti-PD-L1, and anti-CTLA-4.