Blood first line ready screening trial (B-F1RST) and blood first assay screening trial (BFAST) enable clinical development of novel bloodbased biomarker assays for tumor mutational burden (TMB) and somatic mutations in 1L advanced or metastatic NSCLC

Background: Several clinical trials have confirmed the safety and efficacy of atezolizumab (atezo; anti-PD-L1)monotherapy in advanced NSCLC, including in PD-L1-selected 1L patients (pts). Independent of PD-L1 status, high TMB is associated with atezo efficacy. Alectinib is a potent, selective ALK/RET kinase inhibitor currently approved for NSCLC pts previously treated with crizotinib and is expected to have activity in 1L NSCLC pts with ALK or RET alterations. Currently, molecular diagnostics require tumor biopsies which can be difficult to obtain. Here we present trials in progress that aim to clinically evaluate and prospectively validate novel blood-based diagnostic assays that measure TMB in the blood (bTMB) and somatic mutations (e.g., ALK/RET), and to determine the efficacy and safety of 1L atezo or alectinib in NSCLC pts. Trial design: B-F1RST (NCT02848651) is a single-arm study to evaluate the efficacy and safety of atezo and the association between bTMB and efficacy in biomarkerunselected pts. BFAST is a screening and interventional umbrella trial for pts selected based on bTMB or somatic mutations. Eligible pts must have previously untreated, stage IIIB-IVB NSCLC of any histology and measurable disease per RECIST v1.1. Pts will continue treatment until disease progression (all arms) or loss of clinical benefit (atezo only). In B-F1RST, mandatory blood samples will be prospectively collected and retrospectively tested for bTMB. In BFAST, pre-enrollment screening will identify pts who harbor oncogenic somatic mutations (ALK/RET) or are bTMB+(above a prespecified cutoff); pts will be assigned to the appropriate cohort based on screening results. Study treatments and key endpoints are shown in the table. Additional BFAST cohorts may be added in the future to address other somatic mutations. (Table Presented).