Phase II/III blood first assay screening trial (BFAST) in patients (pts) with treatment-naïve NSCLC: Initial results from the ALK+ cohort

Background: Tissue-based assessment of actionable mutations in pts with NSCLC is limited by invasive biopsies and adequacy of biopsied tumour material. Blood-based testing may overcome such limitations, allowing multiplex profiling in a single test. BFAST (NCT03178552) is an ongoing multicentre, open-label, multi-cohort study evaluating the relationship between blood-based next-generation sequencing (NGS) detection of actionable genetic alterations in cell-free DNA, and the activity of targeted therapies and immunotherapy in pts with treatment-naïve advanced NSCLC. We present first results from the ALK+ cohort. Methods: Pts ≥18 years with stage IIIB/IV ALK+ NSCLC (detected by blood-based NGS) received oral alectinib 600mg twice daily. Asymptomatic/treated central nervous system (CNS) metastases were permitted. All pts (with/without CNS disease) had 8-weekly restaging and brain scans. Primary endpoint: confirmed investigator (INV)-assessed objective response rate (ORR; RECIST v1.1). Key secondary endpoints: independent review facility (IRF)-assessed ORR; INV- and IRF-assessed duration of response (DoR), progression-free survival (PFS), overall survival; and safety. Results: Of 2,219 pts screened, blood-based NGS yielded results in 2,188 pts. Overall, 119 pts (5.4%) had ALK+ disease; 87 pts were enrolled and received alectinib. EML4 was the fusion partner in 73 (84%) pts, with TP53 mutations detected in 38 (44%) pts. Median blood-based tumour mutational burden was 2 (range, 0–21). Median follow-up: 12.6 months (range, 2.6–18.7). Confirmed ORR: 87.4% (95% CI 78.5–93.5) by INV and 92.0% (95% CI 84.1–96.7) by IRF. The 12-month INV-confirmed DoR was 75.9% (95% CI 63.6–88.2). In 35 (40%) pts with asymptomatic baseline CNS disease, ORR by INV was 91.4% (95% CI 76.9–98.2). Median PFS: not reached; 12-month PFS by INV was 78.4% (95% CI 69.1–87.7). Safety data were consistent with the known safety profile of alectinib. Conclusions: Blood-based detection of ALK fusions results in high ORR and clinical benefit in pts receiving alectinib. These data validate the clinical utility of blood-based NGS as an additional method to inform clinical decision-making in ALK+ NSCLC. Clinical trial identification: NCT03178552. Editorial acknowledgement: Medical Writing support was provided by Nicola Griffin of Gardiner-Caldwell Communications and funded by F. Hoffmann-La Roche. Legal entity responsible for the study: F. Hoffmann-La Roche Ltd. Funding: F. Hoffman-La Roche Ltd. Disclosure: S.M. Gadgeel: Honoraria (self), Advisory / Consultancy: Ariad, AstraZeneca, Bristol-Myers Squibb, Pfizer and F. Hoffmann-La Roche Ltd/Genentech. T.S.K. Mok: Leadership role: Sanonics Ltd; Honoraria (self), Advisory / Consultancy: ACEA Biosciences, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Chimed, Cirina, Fishawack Facilitate, Ignyta, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, OncoGenex, Pfizer, F. Hoffmann-La Roche Ltd/Genentech, SFJ Pharm; Research grant / Funding (self): AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Merck Sharp & Dohme, Novartis, Pfizer, F. Hoffmann-La Roche Ltd, SFJ Pharmaceutical and XCovery. S. Peters: Honoraria (self), Advisory / Consultancy: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, Eli Lilly, F. Hoffmann-La Roche Ltd, Janssen, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Regeneron and Takeda; Speaker Bureau / Expert testimony: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme, Novartis and Pfizer. J.A.A. Alexander: Honoraria (self), Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim Bristol-Myers Squibb, Pfizer and F. Hoffmann-La Roche Ltd/Genentech, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Takeda. N.B. Leighl: Research grant / Funding (self): F. Hoffmann-La Roche, Array, Guardant and AstraZeneca; Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, F. Hoffmann-Lar Roche, Pfizer; Advisory / Consultancy: Excovery. V. Sriuranpong: Honoraria (self), Advisory / Consultancy: AstraZeneca, Novartis, F. Hoffmann-La Roche Ltd, Pfizer, Sanofi, Eisai, Boehringer, Taiho, Merck Sharp & Dohme, Bristol-Myers Squibb; Research grant / Funding (institution): AstraZeneca, Novartis, F. Hoffmann-La Roche Ltd, Pfizer, Boehringer, Eisai, Taiho, Lilly and Merck Sharp & Dohme. M. Perol: Honoraria (self): F. Hoffmann-La Roche Ltd, AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Takeda, Chugai, Boehringer Ingelheim, Eli Lilly, Amgen and AbbVie. G. De Castro Jr.: Advisory / Consultancy: AstraZeneca, Merck Sharp & Dohme, Bristol-Myers Squibb, F. Hoffmann-La Roche Ltd, Novartis, Boehringer Ingelheim, Pfizer, Bayer; Speaker Bureau / Expert testimony: Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, AstraZeneca, Pfizer, F. Hoffmann-La Roche Ltd, Bayer, TEVA; Travel / Accommodation / Expenses: Merck Sharp & Dohme, Bristol-Myers Squibb, F. Hoffmann-La Roche Ltd, Bayer, Novartis, Boehringer Ingelheim, AstraZeneca, Pfizer and Bayer. E. Nadal: Honoraria (self), Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, F. Hoffmann-La Roche Ltd, Janssen, Merck Sharp & Dohme, Pfizer and Takeda. F. De Marinis: Honoraria (self): F. Hoffmann La Roche Ltd, Bristol-Myers Squibb, AstraZeneca and Merck. J. Han: Honoraria (self): Roche, AstraZeneca, BMS, MSD, Takeda; Advisory / Consultancy: AstraZeneca, BMS, MSD, Lilly, Novartis, Pfizer, Takeda; Research grant / Funding (self): Roche, Pfizer, ONO. M. Yan: Full / Part-time employment: F. Hoffmann-La Roche Ltd. T. Riehl: Full / Part-time employment: Genentech, Inc. E. Schleifman: Full / Part-time employment: Genentech, Inc. S.M. Paul: Full / Part-time employment: Genentech, Inc. S. Mocci: Full / Part-time employment: Genentech, Inc. D. Shames: Full / Part-time employment: Genentech, Inc. M.S. Mathisen: Full / Part-time employment: Genentech, Inc. R. Dziadziuszko: Honoraria (self), Advisory / Consultancy: F. Hoffmann-La Roche Ltd, Pfizer, Boehringer Ingelheim, Clovis Oncology, Novartis, AstraZeneca and Tesaro.