The overarching goal for this protocol is to establish a National Clinical Trials Network (NCTN) mechanism for genomically screening large but homogeneous cancer populations and subsequently assigning and accruing simultaneously to a multi-substudy "Master Protocol". Biomarker-driven sub-studies in this protocol will compare new targeted therapy (TT) or targeted therapy combinations (TTC) to standard of care (SoC) therapy based on designated therapeutic biomarker-drug combinations, with the ultimate goal being approval of new targeted therapies in this setting. In addition, the protocol
includes a "non-match" sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies. This sub-study will compare a non-match therapy (NMT) to SoC also with the goal of approval. We hypothesize that this Master Protocol mechanism will yield definable and measurable efficiencies in terms of improving genomic screening of cancer patients for clinical trial entry, and improved time lines for drug-biomarker testing allowing for inclusion of the maximum numbers of otherwise eligible patients in comparison with currently employed "single screen-single trial" approaches.