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Introduction: This paper presents results from Cohort B (rearranged during transfection [ RET ], fusion-positive) of the Blood First Assay Screening Trial in patients with advanced non-small cell lung cancer (NSCLC) screened for genetic alterations using blood-based next-generation sequencing., Material and Methods: Adults with advanced RET fusion-positive NSCLC received alectinib 900 mg twice daily (BID) in Phase I. Enrolment closed prematurely with Phase II uninitiated., Results: Among eight treated patients, confirmed best overall responses in evaluable patients were stable disease (4/5) and progressive disease (1/5). One dose-limiting toxicity (death, unknown cause) was considered by the investigator to be related to treatment and underlying disease. Serious adverse events (SAEs) occurred in five patients, and SAEs that may be related to treatment occurred in two patients., Conclusions: Alectinib showed limited activity in advanced RET fusion-positive NSCLC, and further investigation was not conducted due to the development of selective RET inhibitors pralsetinib and selpercatinib. No new safety signals were observed, and the safety profile of alectinib was in line with previous reports at the 600 mg BID dose., Competing Interests: R.D: Advisory/consultancy fees from F. Hoffmann- La Roche, Ltd, Foundation Medicine, Pfizer, AstraZeneca, Novartis, Merck Sharp & Dohme, Karyopharm, and Boehringer Ingelheim. Honoraria from F. Hoffmann-La Roche, Ltd, AstraZeneca, and Amgen. Participated in data safety monitoring boards/advisory boards for F. Hoffmann-La Roche, Ltd, AstraZeneca, Amgen, and Merck Sharp & Dohme. N.P: Advisor and honorarium from, and research with, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Foundation Medicine, Gaurdant Health, Merck, MSD, Novartis, NovellusDx, Pfizer, Roche, and Takeda. IP held for Volatile Organic Compounds for Detecting Cell Dysplasia and Genetic Alterations Associated With Lung Cancer; WO/2012/023138. T.M: Received fees for serving on advisory boards and consulting, and speakers fees and institutional grants and research support from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, and Pfizer. Fees for serving on advisory boards and consulting and speakers fees from ACEA Pharma, Amgen, Boehringer lngelheim, Daiichi Sankyo, Fishawack Facilitate, Ltd., Eli Lilly, OrigiMed Co. Ltd., Sanofi- Aventis; owns stock and has received fees for serving on advisory boards and board of directors/leadership roles from HutchMed; institutional grants and research support and fees for serving on advisory boards and consulting from Merck Serono and SFJ Pharmaceutical Ltd.; fees for serving on advisory boards, board of directors/leadership roles and consulting from Lunit, Inc.; fees for serving on advisory boards and for consulting from AbbVie, BerryOncology, Blueprint Medicines Corporation, C4 Therapeutics, CStone Pharmaceuticals, Curio Science, Eisai, Gilead Sciences, Inc., Gritstone Oncology, Inc., Guardant Health, Hengrui Therapeutics Inc., IQVIA, Janssen, lgnyta, Inc., lncyte Corporation, lnivata, Loxo Oncology Inc., Mirati Therapeutics Inc., Puma Biotechnology Inc., Vertex Pharmaceuticals, Yuhan Corporation; speakers fees and fees for consulting from Alpha Biopharma Co., Ltd., Amoy Diagnostics Co., Ltd., AstraZeneca (before 1 January 2019), BeiGene; fees for serving on advisory boards and institutional grants and research support from AstraZeneca, Gl Therapeutics, Inc., Takeda; institutional grants and research support from Roche, XCovery; speakers fees from Daz Group, InMed Medical Communication, Janssen, Liangyihui Network Technology Co., Ltd., Lucence Health Inc., MD Health Brazil, Medscape LLC, Merck Pharmaceuticals HK Ltd., P. Permanyer SL, PeerVoice, Physicians’ Education Resource, PrIME Oncology, Research to Practice, Roche Pharmaceuticals/Diagnostic/Foundation Medicine, Shanghai BeBirds Translation and Consulting Co., Ltd., Taiho, Takeda Oncology, touchIME; fees for consulting from Elevation Oncology, MoreHealth, Qiming Development (HK) Ltd., Roche Pharmaceuticals, Takeda Pharmaceuticals HK Ltd.; fees for serving on advisory boards for Roche/Genentech and Virtus Medical Group; fees for a board of directors/leadership role with AstraZeneca PLC; discloses serving on advisory boards (uncompensated) for geneDecode Co., Ltd.; owns stock from Act Genomics-Sanomics Group and Aurora Tele-Oncology Ltd.; declares uncompensated board of directors/leadership roles with the American Society of Clinical Oncology, Asian Thoracic Oncology Research Group, Chinese Lung Cancer Research Foundation Limited, Chinese Society of Clinical Oncology, Hong Kong Cancer Fund, Hong Kong Cancer Therapy Society, International Association for the Study of Lung Cancer (ending 30 April 2019), St. Stephen’s College and Preparatory School. S.P: Received institutional support for consulting or advising from AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Biocartis, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, eCancer, Eli Lilly, Elsevier, Foundation Medicine, Illumina, Imedex, IQVIA, Incyte, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Merrimack, Novartis, Oncology Education, PharmaMar, Phosplatin Therapeutics, PER, Pfizer, PRIME, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics and Takeda; institutional fees for speaking at company-sponsored public events for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, eCancer, Eli Lilly, Illumina, Imedex, Medscape, Merck Sharp & Dohme, Novartis, PER, Pfizer, Prime, Roche/Genentech, RTP, Sanofi and Takeda; and institutional grants and research support for the conduct of clinical trials from Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, GlaxoSmithKline, Illumina, Eli Lilly, Merck Sharp & Dohme, Merck Serono, Mirati Therapeutics Inc., Novartis, Pfizer, Phosplatin Therapeutics, and Roche/Genentech. S.P.A: Nothing to disclose. J.A: Received consulting fees from F. Hoffmann-La Roche, Ltd, AstraZeneca, Takeda, and Pfizer; honorarium from F. Hoffmann-La Roche, Ltd, AstraZeneca, Takeda; and meetings and/or travel support from F. Hoffmann- La Roche, Ltd, AstraZeneca, and MSD. B.D.V: Nothing to disclose. M.M: Employment at Syneos Health and works as a Study Statistician in FSP model for F. Hoffmann- La Roche, Ltd on a full-time basis. V.B: Roche employee and shareholder. Breath Analysis of Pulmonary Nodules. US20130150261 A1; Apparatus for treating a target site of a body; WO/2015/059646. S.M.S: Genentech employee and Roche shareholder. E.S: Genentech employee and Roche shareholder. T.R: Roche employee and shareholder. M.S.M: Genentech employee and Roche shareholder. S.M.G: Received fees for consulting from Genentech/Roche, Takeda, AstraZeneca, Pfizer, Daiichi Sankyo and Eli Lilly; served on an independent data monitoring committee for AstraZeneca., (Copyright © 2023 Termedia.)

Tumor mutational burden (TMB) is being explored as a predictive biomarker for cancer immunotherapy outcomes in non-small cell lung cancer. BFAST (NCT03178552)-an open-label, global, multicohort trial-evaluated the safety and efficacy of first-line targeted therapies or immunotherapy in patients with unresectable Stage IIIB or IV advanced or metastatic non-small cell lung cancer who were selected for biomarker status using blood-based targeted next-generation sequencing. In the Phase 3 cohort C evaluating blood-based (b)TMB as a biomarker of atezolizumab efficacy, patients with bTMB of ≥10 (N = 471) were randomized 1:1 to receive atezolizumab or platinum-based chemotherapy per local standard of care. Cohort C did not meet its primary endpoint of investigator-assessed progression-free survival in the population with bTMB of ≥16 (hazard ratio, 0.77; 95% confidence interval: 0.59, 1.00; P = 0.053). Adverse events leading to treatment withdrawal occurred in 10% of patients in the atezolizumab arm and 20% in the chemotherapy arm. Adverse events of special interest occurred in 42% of patients in the atezolizumab arm and 26% in the chemotherapy arm. A prespecified exploratory analysis compared the bTMB clinical trial assay with the FoundationOne Liquid Companion Diagnostic assay and showed high concordance between assays. Additional exploration of bTMB to identify optimal cutoffs, confounding factors, assay improvements or cooperative biomarkers is warranted., (© 2022. The Author(s).)