Redman MW, Papadimitrakopoulou VA, Minichiello K, et al. - To address a need for better therapies for squamous non-small-cell lung cancer, the Lung Cancer Master Protocol (Lung-MAP; S1400) was designed to create an infrastructure for biomarker screening and rapid regulatory intent assessment of targeted therapies. This was the first biomarker-driven master protocol started with the US National Cancer Institute. Eligible patients had stage IV or recurrent squamous non-small-cell lung cancer, had previously been treated with platinum-based chemotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2. of 1,674 patients, 1,404 were assigned to a biomarker-driven substudy; 655 actually registered to a substudy. The substudies evaluated taselisib (targeting PIK3CA alterations), palbociclib (cell cycle gene alterations), AZD4547 ( FGFR alteration), rilotumumab plus erlotinib (MET), talazoparib (homologous recombination repair deficiency), and telisotuzumab vedotin (MET). Integrating data from the substudies, response to targeted therapy was evident in 10 (7.0%) of 143 patients, 53 (16.8%) of 315 patients exhibited response to anti-PD-1 or anti-PD-L1 therapy for immunotherapy-naive disease, and response to docetaxel as second line of therapy was shown in three (5.4%) of 56 patients. As per findings, the objective of Lung-MAP (S1400), which was to rapidly address biomarker-driven therapy questions in squamous non-small-cell lung cancer, was met.