All times are listed in CEST (Central European Summer Time)
- Helena A. Yu (New York, United States of America)
- Rina Hui (Sydney, Australia)
LBA51 - Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial
- Jordi Remon Masip (Barcelona, Spain)
Abstract
Background
APPLE is a randomized, non-comparative, open-label, 3-arm, phase II study in patients with common
Methods
We report the results of arm B (gefitinib until the emergence of circulating tumor DNA (ctDNA)
Results
From Nov 2017 to Feb 2020, 52 and 51 patients in 6 countries were randomized to Arm B and C. Most patients were females (75% and 65%), never smokers (71% and 59%) and had
Conclusions
Serial monitoring of ctDNA T790M status in patients with advanced
Legal entity responsible for the study
European Organization for Research and Treatment of Cancer (EORTC).
Funding
AstraZeneca.
Disclosure
J. Remon Masip: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, MSD, Boehringer-Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Janssen, Takeda, Sanofi; Financial Interests, Personal, Expert Testimony: Ose Immunotherapeutics; Non-Financial Interests, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Other, Co-PI of APPLE trial (EORTC-1525): Astra-Zeneca. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi-Sankyo, Eli Lilly, GSK, Janssen, Onxeo, OSE immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals; Financial Interests, Institutional, Research Grant: Genzyme Corporation, Chugai pharmaceutical, EISAI, Inivata, Ipsen, Turning Point Therapeutics. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, AbbVie, BMS, MSD, Novartis, Sanofi, Takeda, Pfizer, PharmaMar. N. Reguart Aransay: Financial Interests, Personal, Advisory Board: Roche, MSD, Takeda, Bayer, Novartis, Sanofi, Janssen, Astra-Zeneca; Financial Interests, Personal, Invited Speaker: Astra-Zeneca, MSD, Boehringer, Guardant, BMS, Pfizer. I. Monnet: Other, Other, invitation to virtual ASCO 2021 and 2022: Pfizer; Other, Other, invitation to ESMO congress 2021 and 2022: Takeda. P. Garrido Lopez: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, sanofi; Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, MSD, Novartis, Pfizer, Roche, Takeda, Novartis, IO Biotech; Financial Interests, Personal, Advisory Board, Spouse: Boehringer Ingelheim, Gebro, Janssen, Nordic; Financial Interests, Personal, Invited Speaker, Spouse: Boehringer Ingelheim, Janssen; Financial Interests, Personal, Other, Data monitoring committee for a clinical trial in 2020: Novartis; Financial Interests, Personal, Other, Lung Cancer Medical Education TASC Committee 2021: Janssen; Financial Interests, Institutional, Invited Speaker: Novartis, Janssen, AstraZeneca, Pfizer, Blue print, Apollomics, Amgen, Array Biopharma; Financial Interests, Personal, Invited Speaker, study entitled JNJ-372: Janssen; Non-Financial Interests, Leadership Role, Council member as Women for Oncology Committee ChairFellowship and Award Committee and Press CommitteeFaculty for lung and other thoracic tumours: ESMO; Non-Financial Interests, Leadership Role, President of the Spanish Federation of Medical Societies (FACME): FACME; Other, My son is working in the pharma company TEVA as an engineer. I do not have any kind of relationship with Teva: Teva; Non-Financial Interests, Leadership Role, Former President of Spanish Medical Oncology SocietyMember of the Spanish National Health Advisory Board: SEOM; Non-Financial Interests, Leadership Role, Member of the Scientific Committee of the Spanish Against Cancer Research Foundation (aecc) and also Borad member: AECC; Non-Financial Interests, Leadership Role, IASLC Women in Thoracic Oncology Working Group Member: IASLC. M.R. Garcia Campelo: Financial Interests, Personal, Invited Speaker: BMS, Jansen, Takeda, pfizer, roche, AstraZeneca, novartis, lilly, AstraZeneca, Jansen; Financial Interests, Personal, Advisory Board: MSD, Jansen, Sanofi, Takeda, BMS, roche, pfizer, AstraZeneca, novartis, lilly. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Sanofi, amgen, Bayer, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: Takeda, Lilly, Jansen, Pfizer, AstraZeneca, Lilly, Amgen, Daiichi, Roche, Roche, JNJ, Mirati; Financial Interests, Institutional, Research Grant: Amgen; Non-Financial Interests, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Member: IASCL, ASCO, AACR. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, SeattleGenetics, Pfizer, Takeda, Regeneron, MSD, Bristol Myers-Squibb, PharmaMar, Bayer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, FoundationMedicine; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Roche, AstraZeneca, MSD, Amgen, Celon Pharma, Pfizer, Novartis, Brsitol Myers-Squibb, Eli Lilly, Loxo; Financial Interests, Invited Speaker: BeiGene, Ardigen, OSE Immunotherapeutics; Financial Interests, Personal and Institutional, Other, Subinvestigator and ad hoc Consultant: PDC* line Pharma; Non-Financial Interests, Institutional, Product Samples: Novartis, Pfizer, AstraZeneca, Roche; Other, Travel: Roche, Bristol Myers-Squibb, AstraZeneca. All other authors have declared no conflicts of interest.
LBA52 - Tepotinib + osimertinib for EGFRm NSCLC with MET amplification (METamp) after progression on first-line (1L) osimertinib: Initial results from the INSIGHT 2 study
- Julien Mazieres (Toulouse, France)
Abstract
Background
A high unmet need exists for effective treatments post 1L osimertinib in NSCLC. For 15–30% of patients (pts) with resistance due to
Methods
In this open-label 2-arm Phase II study, pts with advanced
Results
As of April 26, 2022, among 425 pre-screened pts, *Timeframe for primary analysis. Pts also included in analysis of 48 pts with ≥3 months’ follow-up. †Incomplete post-baseline assessments (n=2), SD <12 weeks (n=3), COVID-19-related early discontinuation (n=1), and PD/AE-related-early discontinuations (n=5).
TEP+OSI TEP TEP+OSI 54.5 (32.2, 75.6) 45.8 (31.4, 60.8) 8.3 (0.2, 38.5) 56.5 (34.5, 76.8) 12 (54.5) 22 (45.8) 1 (8.3) 13 (56.5) 2 (9.1) 5 (10.4) 2 (16.7) 1 (4.3) 4 (18.2) 10 (20.8) 8 (66.7) 5 (21.7) 4 (18.2) 11 (22.9)† 1 (8.3) 4 (17.4)
Conclusions
In this initial analysis of INSIGHT 2, TEP+OSI was highly active and well tolerated in pts with
Clinical trial identification
NCT03940703.
Editorial acknowledgement
Medical writing assistance (funded by Merck Healthcare KGaA, Darmstadt, Germany) was provided by Rebecca Hurst of Syneos Health, London, UK.
Legal entity responsible for the study
Merck Healthcare KGaA, Darmstadt, Germany.
Funding
Merck Healthcare KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).
Disclosure
J. Mazieres: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, MSD, AstraZeneca, Pfizer, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, Amgen, Takeda, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche/Genentech, AstraZeneca, Bristol Myers Squibb. T.M. Kim: Financial Interests, Personal, Advisory Board: AstraZeneca, Hanmi, Janssen, Novartis, Takeda; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Personal, Research Grant: AstraZeneca-KHIDI; Non-Financial Interests, Principal Investigator: AstraZeneca/MedImmune, Boryung, Hanmi, Janssen, Boehringer-Ingelheim, Novartis, Takeda, Sanofi, Roche/Genentech, Merck Sharp & Dohme Corp, Merck Serono, REGENERON, Genmab, Bayer. M. Wislez: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, AstraZeneca, Pfizer, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, Janssen, Roche. C. Dooms: Financial Interests, Personal, Invited Speaker: Amgen, Eli Lilly, Pfizer, Roche, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, Bristol Myers Squibb, MSD; Financial Interests, Personal, Advisory Board: Amgen, Eli Lilly, Pfizer, Roche, Novartis, Merck Healthcare KGaA, Darmstadt, Germany, Bristol Myers Squibb, MSD. G. Finocchiaro: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche, Merck Healthcare KGaA, Darmstadt, Germany, MSD, Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, Merck Healthcare KGaA, Darmstadt, Germany, MSD, Amgen. H. Hayashi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co. Ltd., Bristol Myers Squibb Co. Ltd, AstraZeneca K.K, Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan K.K, Merck Biopharma Co. Ltd, MSD K.K., Novartis Pharmaceuticals K.K, Pfizer, Takeda Pharmaceutical Co. Ltd, Janssen Pharmaceutical K.K.; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb Co. Ltd, Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K, Shanghai Haihe Biopharm, Pfizer, AstraZeneca K.K; Financial Interests, Institutional, Funding: AstraZeneca K.K., Astellas Pharma Inc., MSD K.K., Ono Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Novartis Pharma K.K., grants, Pfizer Japan Inc., Bristol Myers Squibb Company, Eli Lilly Japan K.K., Chugai Pharmaceutical Co.,Ltd., Daiic; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca K.K., Boehringer Ingelheim Japan Inc., Chugai Pharmaceutical Co. Ltd., and Ono Pharmaceutical Co. Ltd.; Non-Financial Interests, Principal Investigator: Ono Pharmaceutical Co. Ltd. and Bristol Myers Squibb Co; Non-Financial Interests, Member: West Japan Oncology Group, Japan Society of Medical Onclogy. C.K. Liam: Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Eli Lilly, MSD, Novartis, Pfizer, Roche. J. Raskin: Financial Interests, Personal, Advisory Role: Pfizer, Eli Lilly; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Bristol Myers Squibb; Financial Interests, Personal, Other, Travel Expense: Roche. L.M. Tho: Financial Interests, Personal, Research Grant: EMD Serono, an affiliate of Merck KGaA; Financial Interests, Personal, Other, Honoraria: Pfizer, Roche, AstraZeneca. F. de Marinis: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Roche, Pfizer. E. Nadal: Financial Interests, Personal, Advisory Role: Merck Healthcare KGaA, Darmstadt, Germany, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi, Takeda; Financial Interests, Personal, Research Grant: Merck Healthcare KGaA, Darmstadt, Germany, Pfizer, Roche, Bristol Myers Squibb. E. Smit: Financial Interests, Institutional, Advisory Role: Eli Lilly, AstraZeneca, Boehringer Ingelheim, Roche/Genentech, Bristol Myers Squibb, Merck Healthcare KGaA, Darmstadt, Germany, MSD Oncology, Takeda, Bayer, Regeneron, Novartis, Daiichi Sankyo, Seattle Genetics; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Bayer, Roche/Genentech, AstraZeneca, Bristol Myers Squibb. X. Le: Financial Interests, Personal, Advisory Role: AstraZeneca, Eli Lilly, Novartis, Daiichi Sankyo, Hengrui Therapeutics, EMD Serono, an affiliate of Merck KGaA; Financial Interests, Personal, Research Grant: Eli Lilly, Boehringer Ingelheim. S. Brutlach: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. A.M. O'Brate Grupp: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. S. Adrian: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. B. Ellers-Lenz: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. N. Karachaliou: Financial Interests, Personal, Full or part-time Employment: Merck Healthcare KGaA, Darmstadt, Germany. Y. Wu: Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Roche, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, Eli Lilly, Pfizer. All other authors have declared no conflicts of interest.
LBA53 - ELIOS: A multicentre, molecular profiling study of patients (pts) with epidermal growth factor receptor-mutated (EGFRm) advanced NSCLC treated with first-line (1L) osimertinib
- Zofia Piotrowska (Boston, United States of America)
Abstract
Background
Osimertinib – a 3rd-generation EGFR-TKI – is the preferred 1L treatment for EGFRm advanced NSCLC; however, pts can eventually develop progressive disease (PD). ELIOS (NCT03239340) characterised resistance mechanisms to 1L osimertinib. To our knowledge, this is the first prospective study with a primary objective comparing paired baseline and post-PD tumour tissue biopsies.
Methods
Pts with EGFR-TKI naïve advanced NSCLC with an EGFR-TKI-sensitising mutation received osimertinib 80 mg QD. Mandatory tumour biopsies were taken pre-treatment and post-PD; samples were analysed by next-generation sequencing. 1º endpoint: proportion of pts with a given tumour genetic and proteomic marker (including, but not limited to, EGFR mutations, HER2 and MET expression and/or amplification [amp]) at PD. 2º endpoints included investigator-assessed PFS (RECIST 1.1) and safety.
Results
154 pts were enrolled (full analysis set; FAS): median age 62 yrs (range 35–87), 77% Asian, Ex19Del/L858R/atypical EGFR mutations 55/38/7%. At data cutoff, 119 pts had PD (24 not progressed; 11 censored for other reasons); of these, 46 (39%) had evaluable paired biopsies. Median PFS (FAS) was 16.4 months (95% CI, 12.7, 20.3). AEs/SAEs occurred in 97/31% of pts. Key genetic alterations (Table) included acquired amp in MET (17%) and NKX2.1 (11%) and acquired EGFR C797S (15%). High frequency mutations at baseline (CDKN2A loss, EGFR amp, EGFR and TP53 mutations) did not differ significantly at PD.
Conclusions
Efficacy and safety of 1L osimertinib were consistent with FLAURA. MET amp was the main acquired resistance mechanism to osimertinib, consistent with previous data. NKX2.1 amp was identified as a potential new resistance marker. Paired biopsies were obtained in only 39% of pts, highlighting the challenges of obtaining post-PD tissue biopsies and the need for more comprehensive non-invasive testing methods. See table. *Defined as mutations detectable at PD that were not detectable at baseline (for an individual patient) Genetic alterations shown were selected based on high-frequency of detection and/or prior knowledge of involvement in osimertinib resistance.
N (%) Baseline (N=46) Progression (N=46) Acquired* (N=46) 2 (4) 9 (20) 10 (22) 11 (24) 9 (20) 11 (24) 7 (15) 10 (22) 0 (0) 7 (15) 4 (9) 9 (20) 13 (28) 11 (24) 3 (7) 6 (13) 0 (0) 2 (4) 0 (0) 1 (2)
Clinical trial identification
NCT03239340.
Editorial acknowledgement
The authors would like to acknowledge Caroline Allinson, BSc, of Ashfield MedComms, an Inizio Company, for medical writing support that was funded by AstraZeneca in accordance with Good Publications Practice (GPP3) guidelines.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
Z. Piotrowska: Financial Interests, Personal, Advisory Board: Janssen, Takeda, Cullinan, C4 Therapeutics, Blueprint, AstraZeneca, EliLilly; Financial Interests, Institutional, Research Grant: Novartis, Takeda, Spectrum, AstraZeneca, Tesaro/GSK, Cullinan, Daiichi, Janssen, Blueprint; Financial Interests, Institutional, Invited Speaker: AbbVie; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: Cullinan; Financial Interests, Personal, Advisory Role: Eli Lilly, Janssen, Daiichi. M. Ahn: Financial Interests, Advisory Board: AstraZeneca, Bristol-Myers Squibb, MSD, Ono Pharmaceutical, Roche, Takeda, Alpha Pharmaceutical; Financial Interests, Other: AstraZeneca, Bristol-Myers Squibb, MSD, Ono Pharmaceutical, Roche. Y.K. Pang: Other, Personal, Principal Investigator: FLAURA and ELIOS trials. S.H. How: Financial Interests, Invited Speaker: AstraZeneca, MSD, Boehringer Ingelheim; Financial Interests, Advisory Board: AstraZeneca, Pfizer, Novartis, Roche, MSD, Boehringer Ingelheim, Takeda; Financial Interests, Research Grant: AstraZeneca, Pfizer, Novartis, Roche, MSD, Boehringer Ingelheim. S. Kim: Financial Interests, Research Grant: AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly, Yuhan; Financial Interests, Other: AstraZeneca, Boehringer Ingelheim, Novartis, Eli Lilly, Roche, BMS. P.J. Voon: Financial Interests, Advisory Board: AstraZeneca, Novartis, MSD, Ipsen, Pfizer. D.L. Cortinovis: Financial Interests, Advisory Board: MSD, BMS, Novartis, Boehringer Ingelheim, Amgen, Roche, Sanofi Genzyme, Takeda; Financial Interests, Invited Speaker: AstraZeneca, Roche. J. De Castro Carpeno: Financial Interests, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Gilead, Hoffmann- La Roche, Merck Sharp and Dohme, Pfizer, Takeda; Financial Interests, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, GSK, Janssen, Lilly, Merck Sharp and Dohme, Novartis, Pfizer, Hoffmann- La Roche, Sanofi, Takeda. M. Tiseo: Financial Interests, Speaker’s Bureau: AstraZeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen, Merck, Sanofi; Financial Interests, Research Grant: AstraZeneca, Boehringer Ingelheim. D. Rodriguez Abreu: Financial Interests, Speaker’s Bureau: Roche, AstraZeneca, Bristol-Myers Squibb, MSD, Eli Lilly, Pfizer, Novartis; Financial Interests, Other: Roche, Bristol-Myers Squibb, MSD, Novartis. S.S. Ramalingam: Financial Interests, Research Grant: Amgen, Advaxis, AstraZeneca, BMS, Merck, Tesaro, Takeda, Genmab; Financial Interests, Other: Amgen, BMS, Genentech, Merck, Tesaro, Takeda, GlaxoSmithKline, AstraZeneca. J. Li: Financial Interests, Full or part-time Employment: AstraZeneca; Financial Interests, Stocks/Shares: AstraZeneca. L. Servidio: Financial Interests, Full or part-time Employment: AstraZeneca; Financial Interests, Stocks/Shares: AstraZeneca. S. Sadow: Financial Interests, Research Grant: Novartis, Takeda, Spectrum, AstraZeneca, Tesaro, Cullinan, Daiichi, AbbVie; Financial Interests, Other: AstraZeneca, Blueprint, Medicine, Janssen, Takeda, Jazz Pharmaceuticals, C4 Therapeutics. R.J. Hartmaier: Financial Interests, Full or part-time Employment: AstraZeneca; Financial Interests, Stocks/Shares: AstraZeneca; Other, Other: Genetech and Foundation Medicine. B.C. Cho: Financial Interests, Advisory Board: Kanaph Therapeutic Inc., Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc.; Financial Interests, Member of the Board of Directors: Interpark Bio Convergence Corp., J Ints Bio; Financial Interests, Stocks/Shares: TheraCanCac Inc., Gencurix Inc., Bridgebio Therapeutics, Kanaph Therapeutic Inc., Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Royalties: Champions Oncology; Financial Interests, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp.; Financial Interests, Advisory Role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines; Financial Interests, Other: DAAN Biotherapeutics.
Invited Discussant LBA51, LBA52 and LBA53
- Helena A. Yu (New York, United States of America)
Q&A
LBA54 - Three years survival outcome and continued cemiplimab (CEMI) beyond progression with the addition of chemotherapy (chemo) for patients (pts) with advanced non-small cell lung cancer (NSCLC): The EMPOWER-Lung 1 trial
- Mustafa Ozguroglu (Istanbul, Turkey)
Abstract
Background
In the EMPOWER-Lung 1 trial, CEMI monotherapy provided a significantly improved overall survival (OS) and an acceptable safety profile vs chemo in pts with newly diagnosed advanced NSCLC. We are reporting the 3-year survival data of the trial. Also, we are presenting the first efficacy data of pts who continued CEMI at progression (PD) with addition of histology-specific chemo.
Methods
Pts were randomized 1:1 to CEMI 350 mg IV every 3 weeks for 2 years or investigator’s choice of chemo. Pts randomized to CEMI with PD, confirmed by a blinded independent review committee (BIRC), were allowed to continue CEMI with the addition of up to 4 cycles of chemo. To be included in the post PD analysis, pts had to receive at least one dose of chemo and have at least one scan following PD on CEMI. Response to continued CEMI + chemo was assessed by BIRC against a new baseline, defined as the last scan prior to the initial dose of chemo.
Results
At median follow-up of 37.1 months (m; range: 24.0 : 56.5), median OS (mOS) was 23.4 m (19.4, 27.4) for CEMI pts (N=357) vs 13.7 m (11.2, 16.2) for chemo pts (N=355), with hazard ratio (HR) of 0.634 (0.524, 0.768); median progression free survival (mPFS) was 6.3 m (4.6, 8.3) vs 5.3 m (4.3, 6.0), HR 0.560 (0.470, 0.666). 64 pts continued CEMI + chemo as 2L therapy. Continued CEMI + chemo as 2L therapy resulted in a 31.3% objective response rate and a mOS of 15.1 m (11.3, 18.7), and was generally tolerated, with 19 pts (29.7%) experiencing serious treatment-emergent adverse event (TEAE), and 3 pts each with TEAE resulting in discontinuation of study treatment or death.
Conclusions
At 3 year follow-up, HRs of CEMI vs. chemo improved (vs at 13 m follow-up) for both PFS and OS despite 76% crossover rate, an exceptional finding in the NSCLC field. Continued CEMI + chemo as 2L therapy provided meaningful and durable ORR and OS benefits and these results compare favorably to historical data of pts receiving chemo alone as 2L therapy (after immune-checkpoint inhibitor monotherapy). This data is the first report from a Phase 3 study providing therapeutic advantage to pts who progress after 1L PD1 monotherapy.
Clinical trial identification
NCT03088540.
Editorial acknowledgement
Medical writing support was provided by Osnat Ben-Shahar PhD from Regeneron.
Legal entity responsible for the study
Regeneron Pharmaceuticals, Inc.
Funding
Regeneron Pharmaceuticals, Inc., and Sanofi.
Disclosure
M. Özgüroğlu: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen, Sanofi, Astellas. A. Sezer: Financial Interests, Institutional, Research Grant: Roche, Merck Sharp & Dohme, Merck Serono, AstraZeneca, Lilly, Novartis, Johnson & Johnson, Regeneron Pharmaceuticals Inc., Sanofi. M. Schenker: Financial Interests, Personal, Research Grant: Bristol-Myers Squibb, Astellas, AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck Serono, Merck Sharpe & Dohme, Novartis, Pfizer, Regeneron, Roche. I. Cicin: Financial Interests, Personal, Advisory Role: AbbVie, Abdi Ibrahim, Bristol-Myers Squibb, Janssen Oncology, Lilly, MSD Oncology, Nobelpharma, Novartis/Ipsen, Pfizer, Roche, Servier, Teva; Financial Interests, Personal, Speaker’s Bureau: Abdi Ibrahim, Bristol-Myers Squibb, Novartis, Pfizer, Roche. G.F. Ho: Financial Interests, Personal, Advisory Board: Merck & Co., Inc., Novartis, AstraZeneca, Boehringer Ingelheim, Pfizer; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Pfizer, Merck & Co., Inc., Novartis, Roche, Boehringer Ingelheim; Financial Interests, Personal, Other, Chairperson: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: EliLily, Regeneron, Merck & Co., Inc., AB Science, Astellas, Tessa Therapeutics, Roche, Arcus Bioscience, AstraZeneca, Pfizer; Non-Financial Interests, Institutional, Product Samples: Pfizer, Eli Lilly, Novartis, Janssen Pharmaceuticals. S. Li: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. J. Pouliot: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. F. Seebach: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. I. Lowy: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. P. Rietschel: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. All other authors have declared no conflicts of interest.
972O - Nivolumab (Nivo) plus ipilimumab (Ipi) 6-months treatment versus continuation in patients with advanced non-small cell lung cancer (aNSCLC): Results of the randomized IFCT-1701 phase III trial
- Gerard Zalcman (Paris, France)
Abstract
Background
1st-line immunotherapy (io) is a standard treatment for patients (pts) with aNSCLC and no targetable mutation. Classical 2-years io duration does not rely on solid evidence. We aimed to assess whether 6-months nivo/ipi duration was equivalent to continuation until progression in pts with disease control (DC).
Methods
In this multicenter non-inferiority randomized phase III trial, eligible pts treatment-naive, age>18, PS 0-1, had histologically proved stage IV NSCLC and measurable disease. They received Nivo 3 mg/kg q2w plus Ipi 1 mg/kg q6w, until progression or unacceptable toxicity. At 6 months, pts with DC and no severe TRAEs were randomized (1:1) into arm A, io continuation, and arm B, observation. At progression, arm A pts received an investigator's choice 2nd line platinum-based chemo, while arm B pts resumed double io. Primary endpoint was progression-free survival (PFS). 450 pts x 2 were to be randomized, to achieve 80% power, with 0.025 one-sided an error. Observing that European filing for the io combo was not submitted, the trial steering committee decided to stop the accrual on Jan. 15th 2021.
Results
From May. 2018 to Jan. 2021, 265 pts (70.6% male, 62.7y median age, 60% stage IVB, 22.3% SCC, 9.9% PDL1≥50%, 12.2% PDL1<1%) were accrued. 137 (72.1%) pts showed disease progression before 6 months, 11 died (5.8%), 29 (15.3%) experienced TRAEs contra-indicating continuation, 13 (6.8%) were deemed ineligible for randomization. 71 pts with DC were randomized. With a median 21.0 months follow-up from randomization, median PFS was 20.8 (8.3-NR) months in arm A, not reached (17.7-NR) in arm B pts. 12-months PFS was 57.1% (39.3-71.5) and 77.6% (58.7-88.7) in arm A and B respectively (p=0.09). Adj.HR (arm B
Conclusions
The non-significant PFS difference between the 6-months and the continuation arms is hypothesis generating since data are underpowered due to trial premature halt.
Clinical trial identification
EudraCT: 2017-002540-33; NCT03469960.
Legal entity responsible for the study
IFCT.
Funding
IFCT BMS.
Disclosure
G. Zalcman: Non-Financial Interests, Personal, Other, Invitations, travel and housing for international meetings: Roche, MSD, BMS, AstraZeneca, Lilly, Pfizer, AbbVie; Financial Interests, Personal, Advisory Board: Lilly, AstraZeneca, BMS, Pfizer, Roche, MSD, Boehringer Ingelheim, Inventiva, Paredox Therapeutics; Financial Interests, Institutional, Principal Investigator: Lilly, GSK, Roche, MSD, Merck-Serono, Pfizer, AstraZeneca, Sanofi-Aventis, Pierre Fabre, Boehringer Ingelheim, BMS, Novartis, Ariad, Takeda. A. Madroszyk Flandin: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche; Financial Interests, Institutional, Advisory Board: BMS; Non-Financial Interests, Personal, Other: MSD. D. Debieuvre: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Janssen, Pfizer, Ose Immunotherapeutics, Novartis, Sanofi-Aventis, Amgen, Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Institutional, Funding: Roche, AstraZeneca, Janssen, MSD, Pfizer, BMS, Lilly, Boehringer Ingelheim, GSK, Chugai, Chiesi, Novartis, Takeda, Bayer, Sanofi-Aventis. E. Pichon: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda; Financial Interests, Personal and Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Roche. E. Giroux-Leprieur: Financial Interests, Personal, Advisory Board: BMS. N. Cloarec: Financial Interests, Personal, Advisory Board: Takeda. V. Westeel: Financial Interests, Personal, Other, Scientific committee and invited speaker: Bristol Myers Squibb; Financial Interests, Personal, Other, advisory board, scientific committee and invited speaker: MSD; Financial Interests, Personal, Advisory Board: Takeda, Amgen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche; Financial Interests, Institutional, Other, local PI and steering committee member: Bristol Myers Squib; Financial Interests, Institutional, Invited Speaker: MSD, Roche; Other, support for meeting attendance: AstraZeneca, Bristol Myers Squib, Sanofi. A.C. Toffart: Financial Interests, Personal, Invited Speaker: BMS, MSD, AstraZeneca; Financial Interests, Personal, Advisory Board: BMS, MSD, AstraZeneca; Non-Financial Interests, Personal, Other, Invitation to congress: AstraZeneca, Roche. All other authors have declared no conflicts of interest.
Invited Discussant LBA54 and 972O
- Martin Reck (Grosshansdorf, Germany)
Q&A
- All Speakers (Lugano, Switzerland)