Should patients with lung cancer with high PD-L1 expression be treated with checkpoint inhibitors alone or a combined checkpoint inhibitor and chemotherapy regimen? Bruna Pellini, MD, Moffitt Cancer Center, Tampa, FL, highlights this as a major unanswered question in the field. The ongoing INSIGNA study (NCT03793179) will address this issue, trialing pembrolizumab alone or with chemotherapy in non-small cell lung cancer. Dr Pellini discusses the currently available data on checkpoint inhibitor and chemotherapy use, comparing various combinations and highlighting key knowledge gaps. This interview took place at the American Society of Clinical Oncology (ASCO) 2021 Virtual Meeting.