1361P - Alectinib for treatment-naïve advanced ALK+ NSCLC selected via blood-based NGS: Updated analyses of outcomes, circulating tumour (ct)DNA and biomarker subgroups from BFAST Cohort A

Background

BFAST (NCT03178552) is an ongoing global, open-label, multicohort study assessing the activity of therapies in patients (pts) with advanced/metastatic NSCLC harbouring actionable genetic alterations identified in ctDNA via NGS. In a previous analysis of the BFAST ALK+ NSCLC cohort, a high overall response rate (ORR) was reported in pts treated with alectinib. We present updated data with longer follow-up, and exploratory correlative ctDNA and biomarker analyses.

Methods

Pts aged ≥18 years with treatment-naïve stage III/IV NSCLC had comprehensive genomic profiling via NGS on ctDNA at screening. Pts with ALK fusions (ALK+) received alectinib 600 mg twice daily. Primary endpoint: investigator (INV)-assessed ORR; key secondary endpoints: INV-assessed progression-free survival (PFS), duration of response (DOR), overall survival (OS), safety. Blood samples for exploratory analyses were collected every 2 cycles during treatment, and at disease progression if feasible.

Results

The cohort included 87 ALK+ pts; median survival follow-up was 52.0 months (range 2.6–62.6). At data cutoff (24 Feb 2023), 34 (39.1%) pts remain on alectinib. Median PFS data for the overall population and per subgroup are presented in the table. In the overall population, ORR was 89.7% (95% CI 81.3–95.2); median DOR was 35.1 months (95% CI 24.8–49.7); 48-month OS rate was 58.3% (95% CI 47.8–68.7). Most pts (93%) had complete clearance of ctDNA (no ALK fusion reads) by Cycle 3 Day 1. Pts without ALK clearance had poor PFS (7.1 months; 95% CI 5.6–NE). No new safety signals were identified.

Conclusions

BFAST is the first trial with mature clinical data using prospective blood-based NGS screening of ALK to select pts for treatment with alectinib. PFS data were consistent with the ALEX study. Concurrent TP53 mutation and high baseline ctDNA levels were associated with poorer prognosis; ctDNA clearance was associated with better outcomes. Table: 1361P

*N=71 patients with Cycle 3 Day 1 data. cTF, composite tumour fraction; NE, not estimable

Clinical trial identification

NCT03178552.

Editorial acknowledgement

This study is sponsored by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance was provided by Laura Vergoz, PhD, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

S.M. Gadgeel: Financial Interests, Personal, Other, Travel: Mirati; Financial Interests, Personal, Advisory Board: Genentech/Roche, AstraZeneca, Mirati, Pfizer, Blueprint, Takeda, Bristol Myers Squibb, Merck, Eisai, Gilead, GSK, Arcus. T.SK. Mok: Non-Financial Interests, Personal, Advisory Board, Uncompensated: geneDecode Co. Ltd; Financial Interests, Personal, Stocks/Shares: HutchMed, Act Genomics- Sanomics Group, Aurora Tele-Oncology Ltd; Non-Financial Interests, Personal, Member of Board of Directors, Uncompensated: 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 & Preparatory School; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Acea Pharma, Amgen, Boehringer lngelheim Pharmaceuticals, Inc., Daiichi Sankyo, Inc., Fishawack Facilitate, Ltd., Lilly, OrigiMed Co. Ltd., Sanofi-Aventis, HutchMed, Merck Serono, C4 Therapeutics, Inc, CStone Pharmaceuticals, Curio Science, Eisai, Gilead Sciences, Inc., Gritstone Oncology,Inc., Guardant Health, Hengrui Therapeutics Inc., IQVIA, Janssen, lgnyta, Inc., lncyte Corporation, lnivata, SFJ Pharmaceutical Ltd, Lunit, Inc., AbbVie Inc., BerryOncology, Blueprint Medicines Corporation, Loxo Oncology Inc., Mirati Therapeutics Inc., Puma Biotechnology Inc., Vertex Pharmaceuticals, Yuhan Corporation, AstraZeneca, Gl Therapeutics, Inc., Takeda, Roche/Genentech, Virtus Medical Group; Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Acea Pharma, Amgen, Boehringer lngelheim Pharmaceuticals, Inc., Daiichi Sankyo, Inc., Fishawack Facilitate, Ltd., Lilly, OrigiMed Co. Ltd., Sanofi-Aventis, Merck Serono, SFJ Pharmaceutical Ltd, Lunit, Inc., AbbVie Inc., BerryOncology, Blueprint Medicines Corporation, C4 Therapeutics, Inc, 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, Alpha Biopharma Co., Ltd., Amoy Diagnostics Co., Ltd., AstraZeneca (before 1 January 2019), BeiGene, Daz Group, InMed Medical Communication, Janssen Pharmaceutica NV, 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 One, Shanghai BeBirds Translation and Consulting Co., Ltd., Taiho, Takeda Oncology, touchIME, Elevation Oncology, MoreHealth, Qiming Development (HK) Ltd., Roche Pharmaceuticals, Takeda Pharmaceuticals HK Ltd.; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pfizer, Merck Serono, SFJ Pharmaceutical Ltd, AstraZeneca, Gl Therapeutics, Inc., Takeda, Roche, XCovery; Financial Interests, Personal, Member of Board of Directors: HutchMed, Lunit, Inc., AstraZeneca PLC. S. Peters: Financial Interests, Institutional, Invited Speaker: AiCME, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, GSK, Illumina, Imedex, Ipsen, Medscape, Merck Sharp and Dohme, Mirati, Novartis, PER, Peerview, Pfizer, Roche/Genentech, RTP, Sanofi, Takeda; Financial Interests, Institutional, Advisory Board: AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, BerGenBio, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack, Foundation Medicine, Genzyme, Gilead, GSK, Hutchmed, Illumina, Imedex, IQVIA, Incyte, Ipsen, iTeos, Janssen, Medscape, Medtoday, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Novocure, OncologyEducation, Pharma Mar, Promontory Therapeutics, Per, Peerview, Pfizer, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Vaccibody; Financial Interests, Institutional, Member of Board of Directors: Galenica; Financial Interests, Institutional, Principal Investigator: Trials sponsored by Amgen, Arcus, AstraZeneca, BeiGene, Bristol Myers Squibb, GSK, iTeos, Merck Sharp and Dohme, Mirati, Pharma Mar, Promontory Therapeutics, Roche/Genentech , Trial sponsored by Seattle Genetics; Other, Personal, Member: ESMO, ASCO, AACR, IASLC, SSOM, SAKK, ETOP; Other, Personal, Leadership Role: Vice President Swiss Cancer League, past President ESMO, Strategic Advisory board SPCC (Paris Saclay) Chair, ETOP scientific chair. E. Nadal: Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Sanofi, Pfizer, Lilly, Amgen, Janssen, AstraZeneca, Takeda, Sanofi, Qiagen; Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Merck- Serono, Sanofi, Pfizer, Lilly, Amgen, Janssen, Daiichi Sankyo, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, Qiagen and Bayer; Non-Financial Interests, Personal, Research Grant: Roche, Pfizer, Merck-Serono, Bristol Myers Squibb; Other, Personal, Principal Investigator: Roche. J. Han: Financial Interests, Personal, Invited Speaker: Janssen, Novartis, Merck, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Amgen, Abion; Financial Interests, Personal, Sponsor/Funding: Pfizer, Roche, Takeda, Ono; Financial Interests, Personal, Advisory Role: Takeda, Merck. J.A. Alatorre Alexander: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Roche, Takeda, BMS, Amgen; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD, Roche, Takeda, BMS, Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Roche, Takeda, BMS, Amgen. N. Leighl: Financial Interests, Institutional, Research Grant, Institutional grant: F. Hoffmann-La Roche Ltd. V. Sriuranpong: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, Pfizer, Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, MSD, Amgen; Financial Interests, Personal, Advisory Role: Roche, MSD, Takeda, AstraZeneca, Novartis, Amgen. M. Pérol: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, Takeda, BMS, AstraZeneca, Amgen, MSD, Sanofi, Janssen-Cilag, Daiichi Sankyo, Medscape; Financial Interests, Personal, Expert Testimony: Roche, AstraZeneca, BMS; Financial Interests, Personal, Advisory Board: Roche, Eli Lilly, Pfizer, Merck Sharp & Dohme, Bristol Myers Squibb, Novartis, AstraZeneca, Takeda, Gritstone, Sanofi, GSK, Amgen, Daïchi- Sankyo, Janssen-Cilag, Ipsen, AnHeart Therapeutics, Eisai; Other, Personal, Principal Investigator: Roche, Eli Lilly, Pfizer, Merck Sharp & Dohme, Bristol Myers Squibb, Novartis, AstraZeneca, Takeda, Amgen, Daïchi-Sankyo, AnHeart Therapeutics, AbbVie; Financial Interests, Personal, Sponsor/Funding: Roche, AstraZeneca, Chugai, Takeda, Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Roche, Eli Lilly, Pfizer, Merck Sharp & Dohme, Bristol Myers Squibb, AstraZeneca, Takeda, GSK, Ipsen, AnHeart Therapeutics. G.D. Castro: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Janssen, Merck Serono, Merck Sharp Dohme, Novartis, Pfizer, Roche, Bayer, Takeda; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Janssen, Merck Serono, Merck Sharp Dohme, Novartis, Pfizer, Roche, Bayer, Lilly, Amgen, Sanofi, Takeda; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Bristol Myers Squibb, Janssen, Merck Serono, Merck Sharp Dohme, Novartis, Pfizer, Roche, Bayer, Lilly, Amgen, Sanofi, Takeda, Daiichi Sankyo, GSK, BeiGene; Financial Interests, Personal, Other, Travel and/or accommodations: AstraZeneca, Merck Serono, Merck Sharp Dohme, Novartis, Pfizer, Roche, Bayer, Lilly. F. de Marinis: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Roche, Novartis, Merck. D.S.W. Tan: Financial Interests, Personal, Invited Speaker: Amgen, Bayer, Merck, Pfizer, Novartis, Boehringer Ingelheim, Roche, Takeda ; Financial Interests, Personal, Research Grant: ACM Biolabs, Amgen, AstraZeneca, Bayer and Pfizer; Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, DKSH, GSK, Merck, Novartis, Pfizer, Roche and Takeda. S. Paul: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Roche. Z.J. Assaf: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Roche. M. MacLennan: Financial Interests, Personal, Full or part-time Employment: I am employed by Syneos Health and work on this study as a Study Statistician in FSP model for Roche on a part time basis. T.O. Lohmann: Financial Interests, Personal, Full or part-time Employment: Roche. M.S. Mathisen: Financial Interests, Personal, Full or part-time Employment: Roche/Genentech; Financial Interests, Personal, Stocks/Shares: Roche/Genentech. V. Bhagawati-Prasad: Financial Interests, Personal, Other, Employee: Roche. R. Dziadziuszko: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Novartis, Pfizer, MSD, Amgen; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, Amgen, Bristol Myers Squibb. All other authors have declared no conflicts of interest.