Abstract 12P
Background
ABC-lung explores the potential synergistic effect of combining atezolizumab and bevacizumab with pemetrexed (ABPem) or carboplatin/paclitaxel (ABCPac) in pts with EGFR-mutant NSCLC, resistant to tyrosine kinase inhibitors (TKIs).
Methods
ABC-lung is a 1:1 randomised, non-comparative, international phase II trial evaluating atezolizumab (1200 mg, Q3W) and bevacizumab (15mg/kg, Q3W) until progression (PD) with either carboplatin (AUC5, Q3W) and paclitaxel (175-200 mg/m2, Q3W) 4-6 cycles or pemetrexed (500 mg/m2, Q3W) until PD. The study was stratified by prior treatment with a 3rd-generation EGFR TKI and aimed to improve the 1-year (1y) progression-free survival (PFS) rate from 18% to 37%, assessed per RECIST v1.1 and tested separately in each arm. To reject the null hypothesis, at least 14 of 45 evaluable pts in each arm needed to be progression-free at 1y (power 83%, 1-sided a=0.023, exact binomial test). Secondary endpoints included overall survival (OS), objective response rate (ORR), PFS, quality of life (QoL) and adverse events (AEs).
Results
From 09/2020-09/2022, 95 pts were randomised to account for potential attritions: 45 to ABCPac, and 50 to ABPem. Median age was 62 years, 63% of pts were females, 60% never smokers, 55% Asians, 60% had an exon 19 deletion and 33%/66% had stage IVa/IVb NSCLC. From the 43 evaluable pts with ABCPac and the 45 with ABPem, 9 and 11 pts reached 1y without progression, respectively, missing the success criterion of 14 pts. The 1y PFS rate for randomised pts (median follow-up 19 months, m) was 25% for both ABCPac and ABPem, with median PFS of 6.4m and 7.6m, median OS of 15.4m and 15.6m and ORR of 47% and 32%, respectively. The median number of cycles for bevacizumab and atezolizumab was 8-9. Grade≥3 treatment-related AEs were experienced by 50% of pts with ABCPac and 42% with ABPem. There were no grade 5 AEs. Results from QoL and PD-L1 testing will be included in the presentation.
Conclusions
The observed 1y PFS rate with atezolizumab, bevacizumab in combination with either carboplatin-paclitaxel or pemetrexed was similar in both arms and below the aspired rate of 37%. The safety is consistent with the known toxicity profiles.
Clinical trial identification
NCT04245085.
Legal entity responsible for the study
ETOP IBCSG Partners Foundation.
Funding
F. Hoffmann-La Roche AG.
Disclosure
M. Frueh: Financial Interests, Institutional, Advisory Board: BMS, AstraZeneca, MSD, Takeda, Roche, Eli Lilly, Boehringer Ingelheim, Novartis, Amgen; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca. R.A. Soo: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Lily, Merck, Novartis, Pfizer, Roche, Taiho, Takeda, Yuhan, Janssen, Merck Serono, Puma Biotech, Thermo Fisher; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Pfizer. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Medpacto, Blueprint medicines, RandBio, Hanmi, GC Cell, Gilead, Ridgeline Discovery GmbH; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio Therapeutics, Cyrus Therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen, AstraZeneca, Regeneron, Seagen, Samsung Bioepis; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, Gradiant Bioconvergence, Therapex, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ Bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, JINTSbio, Hanmi, Daewoong Pharmaceutical Co., Ltd., Vertical Bio AG, Korea Institute of Oriental Medicine, National Research Foundation of Korea, KHIDI; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd. M. Majem: Financial Interests, Personal, Advisory Board: Amgen, Roche, AstraZeneca, Takeda, Janssen, Cassen Recordati, Bms, Sanofi; Financial Interests, Personal, Invited Speaker: Amgen, Roche, AstraZeneca, Pfizer, Takeda, Helsinn; Financial Interests, Institutional, Funding: Bms, AstraZeneca, Roche; Non-Financial Interests, Personal, Leadership Role, Board Member: Associacio Contra El CANCER BARCELONA. D. Rodriguez Abreu: Financial Interests, Personal, Advisory Board:MSD, Novartis, Roche/Genentech, Pfizer, Bristol Myers Squibb, AstraZeneca, Regeneron, Gilead, Sanofi, Amgen, Takeda, Eli Lilly, Incyte, Merck Serono; Financial Interests, Personal, Invited Speaker: MSD, Novartis, Roche/Genentech, Pfizer, Bristol Myers Squibb, AstraZeneca, Regeneron, Gilead, Sanofi, Amgen, Takeda, Eli Lilly, Merck Serono; Financial Interests, Personal, Other, Travel expenses: MSD, Novartis, Roche/Genentech, Pfizer. A. Callejo Perez: Financial Interests, Personal, Advisory Board: Boehringer, Pfizer, BMS; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Other, Travel accommodation: MSD; Financial Interests, Personal, Other, Travel accommodation: Takeda. M. Domine Gomez: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD oncology, Roche, Takeda; Financial Interests, Institutional, Advisory Board: Pfizer. M. Provencio Pulla: Financial Interests, Personal, Advisory Board: BMS, MSD, Bayer, Lilly, Roche, Takeda, Janssen; Non-Financial Interests, Personal, Leadership Role, President of Spanish Lung cancer Group: President; Non-Financial Interests, Personal, Leadership Role, Insutituto Investigación Sanitaria Puerta de Hierro: Director. A. Addeo: Financial Interests, Institutional, Advisory Board: BMS, AZD, Roche, Eli Lilly; Financial Interests, Personal, Advisory Board: Pfizer, Takeda, MSD; Financial Interests, Institutional, Invited Speaker: Novartis. J. Han: Financial Interests, Personal, Advisory Board: Norvatis, Lantern, Takeda, Janssen, Merck, Pfizer, Amgen, AstraZeneca, Oncobix; Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, Merck, Roche, Yuhan, Pfizer, Norvatis, AstraZeneca. U. Dafni: Financial Interests, Personal, Other, Member of the Tumor Agnostic Evidence Generation working Group: Roche; Financial Interests, Personal, Expert Testimony, Statistical review and assessment of a Clinical Trial: AstraZeneca; Non-Financial Interests, Personal, Leadership Role, Member of the BoD & Manager of this not for profit organization providing statistical expertise and support in Clinical trials, primarily in cancer: FRONTIER SCIENCE FOUNDATION - HELLAS. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GSK, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, Oncology Education, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology and Deputy Editor Lung Cancer: Elsevier; Financial Interests, Institutional, Advisory Board, Permanent independent scientific advisor: Hutchmed; Financial Interests, Institutional, Member of Board of Directors, Swiss network of pharmacies: Galenica; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A:MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: PharmaMar; Financial Interests, Institutional, Invited Speaker, phase I/II trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Personal, Officer, ESMO President 2020-2022: ESMO; Non-Financial Interests, Personal, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Personal, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Personal, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Personal, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK; Non-Financial Interests, Personal, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Personal, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Personal, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Personal, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Personal, Member, Association of Swiss interns and residents: ASMAC/VSAO. R.A. Stahel: Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, MSD, Pfizer, Roche, GSK, Eisai, Guardant, Merck, Novocure, PharmaMar; Financial Interests, Personal, Other, Editor in Chief: Lung Cancer; Financial Interests, Personal, Other, Editor: CTR; Financial Interests, Institutional, Research Grant, ETOP study: Roche, AstraZeneca, BMS, MSD, Pfizer, Mirati, Janssen, Amgen; Financial Interests, Institutional, Research Grant, IBCSG study: Novartis, Ipsen, Pierre Fabre, MSD, Pfizer, Roche, AstraZeneca, Celgene; Non-Financial Interests, Personal, Member of Board of Directors, PresidentFoundation Council: ETOP IBCSG PartnersFoundation. All other authors have declared no conflicts of interest.