1281O - Atezolizumab (atezo) vs platinum-based chemo in blood-based tumour mutational burden-positive (bTMB+) patients (pts) with first-line (1L) advanced/metastatic (m)NSCLC: Results of the Blood First Assay Screening Trial (BFAST) phase III cohort C

Background

TMB is a promising biomarker for immunotherapy in NSCLC, but current data are mostly retrospective. As not all pts may have sufficient tissue for comprehensive biomarker testing, bTMB was prospectively tested as a novel biomarker using targeted next-generation sequencing. BFAST (NCT03178552), a global, open-label, multi-cohort trial, evaluated safety and efficacy of targeted therapies or immunotherapy in biomarker-selected pts with unresectable mNSCLC. Here we present results from Cohort C of 1L atezo vs platinum-based chemo in pts with bTMB+ mNSCLC.

Methods

We planned to randomise ≈440 pts with 1L mNSCLC with measurable disease per RECIST 1.1 and bTMB ≥10 (9.1 mut/Mb; FMI bTMB assay) 1:1 to atezo 1200 mg IV every 3 weeks or chemo and stratified by tissue availability, ECOG PS, bTMB and histology. The primary endpoint was INV-PFS per RECIST 1.1 in bTMB ≥16 (14.5 mut/Mb) pts. Key secondary endpoints included OS in bTMB ≥10 (intent to treat, ITT) and bTMB ≥16 pts, and INV-PFS in ITT pts.

Results

471 pts were assigned to atezo (n=234) or chemo (n=237). At baseline, 72% had non-squamous histology, 2% never smoked and median SLD was 103 mm. 145 pts with bTMB ≥16 were assigned to atezo and 146 to chemo. At data cutoff (21 May 2020) minimum follow up was 6 mo. INV-PFS difference in bTMB ≥16 pts for atezo vs chemo was not significant (P=0.053; Table). Grade 3-4 TRAEs occurred in 18% (atezo) vs 46% (chemo) of pts. Serious TRAEs occurred in 12% (atezo) vs 14% (chemo). Results at other bTMB thresholds and by F1L CDx will also be presented as an exploratory analysis.

Conclusions

The primary PFS endpoint in bTMB ≥16 pts was not met. OS was numerically better with atezo vs chemo but the difference was not statistically significant. The safety profile of atezo vs chemo was favourable and consistent with atezo monotherapy across indications. Table: 1281O

F1L CDx, FoundationOne Liquid companion diagnostic; FMI, Foundation Medicine, Inc.; INV-PFS, investigator-assessed progression-free survival; OS, overall survival; SLD, sum of longest diameters; TRAE, treatment-related adverse event. ^a Cisplatin/carboplatin + pemetrexed (non-squamous) or cisplatin/carboplatin + gemcitabine (squamous). ^b Stratified Cox HR. Brookmeyer-Crowley 95% CIs. ^c Not formally tested.

Clinical trial identification

NCT03178552.

Editorial acknowledgement

Medical writing support for this abstract was provided by Chris Lum, PhD, of Health Interactions Inc and 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

R. Dziadziuszko: Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Roche, AstraZeneca, Pfizer, MSD, BMS, Boehringer Ingelheim, Takeda, Foundation Medicine, Seattle Genetics, Beigene, Regeneron. S. Peters: Consultation / Advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F. Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp & Dohme, Merck Serono, Merrimack, Mirati, Novartis, PharmaMar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody Talk in a company’s organized public event: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp & Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda. Receipt of grants/research supports: (Sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, F. Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp & Dohme, Merck Serono, Mirati, Novartis, Pfizer, Phosplatin Therapeutics. S.M. Gadgeel: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche/Genentech, Takeda, Pfizer, Bristol Myers Squibb, Novartis, Janssen, Merck, Eli Lilly, Blueprint; Non-Financial Interests, Personal, Other, Serve on IDMC of a phase III trial: AstraZeneca. M.S. Mathisen: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche/Genentech. S.M. Shagan: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Roche. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Merck Serono, Peptomyc, Pfizer, Puma, Regeneron, Sanofi, Syneos Health, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medscape, Merck Sharpe & Dohme, Merck Serono, Peervoice, Pfizer, Springer, Touch Medical; Financial Interests, Personal, Other: Medical Trends; Non-Financial Interests, Personal, Leadership Role, Dr. Felip is President Elect (2021-2023) of Spanish Society of Medical Oncology; Non-Financial Interests, Personal, Member, Dr. Felip is member of the ESMO Nominating Committee and Compliance Committee: ESMO; Non-Financial Interests, Personal, Member, Dr. Felip is member of the Scientific Committee: ETOP; Non-Financial Interests, Personal, Leadership Role, Dr. Felip is member of the Board of Directors and the Executive Committee (2017- September 2021): IASLC. A. Morabito: Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Boehringer Ingelheim, Pfizer, BMS; Financial Interests, Personal, Expert Testimony: Roche, AstraZeneca, Boehringer Ingelheim, Pfizer, BMS; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Eli Lilly, Takeda, MSD. P. Cheema: Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Roche, Pfizer, EMD (Serono), Bristol Myers Squibb, Takeda, Merck; Financial Interests, Institutional, Other, Honoraria: AstraZeneca, Merck; Financial Interests, Institutional, Research Grant, Research Grant/Funding: Merck, AstraZeneca, BMS. C.H. Barrios: Financial Interests, Personal, Advisory Board, Consulting scientific presentations: AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GSK, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, Zodiac; Financial Interests, Personal, Ownership Interest, Pathology Lab: Biomarker; Financial Interests, Personal, Stocks/Shares, Clinical Research Company: MedSIR; Financial Interests, Personal, Stocks/Shares, Application: Tummi; Financial Interests, Institutional, Research Grant: AB Sciences, AbbVie, Abraxis, Amgen, Asana, Astellas, AstraZeneca, BioMarin, BMS, Boehringer Ingelheim, Daiichi Sankyo, Exelixis, GSK, IMclone, Leo Pharma, Lilly, Medivation, Merck KGaA, Merck, Merrimack, Millennium, Mylan, Novartis, Pfizer, PharmaMar, Pol. P. Danchaivijitr: Financial Interests, Personal, Advisory Role, Advisory/Consultancy: MSD, Roche, BMS; Financial Interests, Institutional, Research Grant, Research Grant/Funding: MSD, Roche, AstraZeneca. M. Johnson: Financial Interests, Institutional, Advisory Board: AbbVie, Amgen, Daiichi Sankyo, Editas Medicine, Eisai, G1 Therapeutics, GlaxoSmithKline, Ideaya Biosciences, Incyte, Ribon Therapeutics, and Roche; Financial Interests, Principal Investigator: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, Boehringer Ingelheim, Calithera, Checkpoint Therapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Drac; Financial Interests, Principal Investigator: Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Merck, Mirati, Neovia Oncology, Novartis, OncoMed, Pfizer, PMV Pharmaceuticals, Regeneron, Ribon, Rubius, Sanofi, Seven & Eight Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem Cent; Financial Interests, Institutional, Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, CytomX, EMD Serono, Genentech, Gritstone Oncology, Janssen, Lilly, Merck, Mirati, Novartis, Pfizer, Sanofi-Aventis and WindMIL Therapeutics. S. Novello: Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Sanofi, Eli Lilly, Boehringer Ingelheim, Pfizer, Beigene, BMS; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly, AstraZeneca, Roche, Takeda, MSD; Financial Interests, Personal, Expert Testimony: Eli Lilly, AstraZeneca, Roche, Takeda, MSD. D.R. Gandara: Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Genentech, Merck; Financial Interests, Institutional, Advisory Board, Advisory/Consultancy: AstraZeneca, Roche/Genentech, Guardant Health, IO Biotech, Oncocyte; Financial Interests, Personal, Advisory Board, Advisory/Consultancy: Inivata, Lilly, Merck, Novartis. E. Schleifman: Financial Interests, Personal, Stocks/Shares: Genentech/Roche; Financial Interests, Personal, Full or part-time Employment: Genentech/Roche. J. Wang: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech/Roche. T.S.K. Mok: Financial Interests, Personal, Other, Honoraria: Abbie, Inc., ACEA Pharm, Alpha Biopharma Co. Ltd., Amgen, Amoy Diagnostics Co. Ltd., AstraZeneca, BeiGene, Berry Oncology, Boehringer Ingelheim, Bristol Myers Squibb, Blueprint Medicines Corporation, CStone Pharmaceuticals, Curio Science, Daiichi Sankyo, E; Financial Interests, Personal, Advisory Role, Advisory/Consultancy: Abbie, Inc., ACEA Pharm, Alpha Biopharma Co. Ltd., Amgen, Amoy Diagnostics Co. Ltd., AstraZeneca, BeiGene, Berry Oncology, Boehringer Ingelheim, Bristol Myers Squibb, Blueprint Medicines Corporation, CStone Pharmaceuticals, Curio Science, Daiichi Sankyo, E; Financial Interests, Personal, Other, Lecture: ACEA Pharma, Alpha Biopharma Co. Ltd., Amoy Diagnostics Co. ltd., Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Fishawack Facilitate Ltd., InMed Medical Communication, Lilly, MD Health (Brazil), Medscape/WebMD, Merck Serono, Merck Sharpe & Dohme, Financial Interests, Institutional, Research Grant: Clovis Oncology, SFJ Pharmaceuticals, XCovery; Other, Other, Non-remunerated Activities: geneDecode; Financial Interests, Personal, Stocks/Shares: Lunit Inc., Aurora Tele-Oncology Ltd., Sanomics Ltd.; Financial Interests, Personal, Leadership Role, Board of Directors/Office: Aurora Tele-Oncology Ltd., Hutison Chi-Med, Sanomics Ltd., AstraZeneca PLC.All other authors have declared no conflicts of interest.