Possible explanations may include insufficient synergy of dual inhibition of CTLA‐4 and PD‐1 in NSCLC, limited efficacy of CTLA‐4 blockade in NSCLC, inappropriate dosing and interval of ipilimumab, lack of established predictive biomarkers (given that both PD‐L1 and tumor mutation burden failed), unbalanced post‐progression treatment, and unequal performance of chemotherapy arms across different studies. The gene discussed is CTLA4; the disease is neoplasm.