Background: Targeting of oncogenic driver alterations has proven to be an effective clinical approach across many tumor types. As a result of the approval of targeted therapies against oncogenic driver alterations, molecular biomarker testing is commonly recommended for patients with advanced/metastatic non-small cell lung cancer (NSCLC) before initiation of first-line treatment. Although there are emerging clinical trial data using targeted therapies in patients with early-stage NSCLC, currently molecular biomarker testing is not universally performed as part of routine clinical practice in the early-stage setting. Screening platforms can be utilized to provide comprehensive, validated biomarker testing to facilitate access to clinical trials for appropriate investigational therapies, based on biomarker status. This type of approach aims to be more efficient and to streamline patient recruitment and improve patient access to clinical trials where biomarker testing is not currently performed as part of routine care, especially when the biomarkers of interest are at low prevalence. Methods: This global, non-Investigational Medicinal Product (non-IMP), multicenter master screening study (NCT05419375) provides centralized tissue-based testing to determine patients’ biomarker eligibility for linked Roche clinical trials. Currently this study is only open to screening patients for a linked platform study in unresectable stage III NSCLC (NCT05170204). However, it is envisaged that this screening study will be expanded to support additional clinical trials and indications in the future. Eligible patients must be aged ≥18 years with locally advanced, unresectable stage III NSCLC (according to AJCC 8^th edition), an ECOG PS of 0–2, confirmed availability of a formalin-fixed paraffin-embedded tumor specimen obtained prior to chemoradiation, and adequate hematologic and end-organ function. If a patient is found to have an oncogenic driver mutation and is considered a good candidate for a linked clinical trial, the investigator may propose that they be screened into the respective study. Tumor tissue samples will be centrally tested by validated molecular tests for the presence of specific genetic alterations: EGFR, ALK, ROS1, KRAS, BRAF, HER2, RET, MET, and NTRK1/2/3. Immunohistochemistry may also be performed to determine PD-L1 expression as required by the linked trial eligibility criteria. The primary objective of this screening trial is to determine the biomarker status of patients and their eligibility to participate in a linked clinical trial. Exploratory objectives include characterization of biomarker profiles and patients’ subsequent treatment. No therapeutic intervention will be administered in this study. Enrolment is ongoing across 51 sites in ten countries, with a target enrolment of 15,000 patients. As of 9 February 2023, 27 patients have been enrolled. Clinical trial information: NCT05419375.