Abstract 16P
Background
Platinum-based chemotherapy (chemo) after progression on anti-PD-(L)1 monotherapy leads to limited progression free survival (PFS) of ~3–4 months per historical data. The EMPOWER-Lung 1 study was designed to allow continuation of cemiplimab after progression with the addition of 4 cycles of platinum-based chemo as a new alternative. Here, we report the results of patients who received this treatment.
Methods
EMPOWER-Lung 1 is a multicentre, open-label, randomized, phase III study of patients with treatment-naïve squamous or nonsquamous NSCLC with PD-L1 ≥50%. Patients were randomized 1:1 to cemiplimab 350 mg IV every 3 weeks for 2 years or histology appropriate platinum-based chemo. This exploratory analysis includes 73 patients who had at least 1 scan following progression on cemiplimab and received at least 1 dose of chemo. Most patients had PD-L1 levels between 50% and 89% with few ≥90%. Response was assessed by an independent review committee against a new baseline, defined as the last scan prior to the initial dose of chemo.
Results
In the continued treatment phase with addition of chemo, the objective response rate of 27.4% was slightly lower than 35.6% observed during the initial cemiplimab monotherapy phase. However, median PFS (6.4 months [m] vs 4.8 m) and duration of response (11.5 m vs 7.7 m) were higher in the continued phase vs initial phase. Median overall survival from the time of randomization was 27.4 m (including 15.1 m after addition of chemo) which compares favorably to the 23.4 m in the overall study population. Patient level analysis indicated that benefit beyond progression was observed irrespective of responses to 1L cemiplimab monotherapy. Grade (Gr) ≥3 treatment-emergent adverse events (TEAEs) occurred in 35.6% (26/73) of patients and Gr ≥3 immune-mediated AEs occurred in 2.7% (2/73) of patients. These are generally consistent with the safety profile of cemiplimab plus chemotherapy, with no new safety signals in the extended treatment phase.
Conclusions
This prespecified analysis of continued cemiplimab beyond progression with the addition of platinum-based chemo showed longer PFS compared with historical data for chemo alone without new safety signals.
Clinical trial identification
NCT03088540; R2810-ONC-1624, 2017-03-16.
Editorial acknowledgement
This study was funded by Regeneron Pharmaceuticals, Inc. and Sanofi. Medical writing support was provided by Anil Sindhurakar, PhD and Qing Zhou, ELS, PhD of Regeneron Pharmaceuticals, Inc.
Legal entity responsible for the study
The authors.
Funding
Regeneron Pharmaceuticals, Inc.
Disclosure
M.C. Garassino: Financial Interests, Personal, Advisory Board: Eli Lilly, SeaGen International GmbH, Eli Lilly, Incyte, GSK, Bayer Healthcare Pharmaceuticals, Blueprint Medicines, AstraZeneca and Daiichi Sankyo Oncology Teams, Roche, Daiichi Sankyo, Mirati Therapeutics, Inc, Daiichi Sankyo/AstraZeneca, AstraZeneca Poland, Daiichi Sankyo, Inc., MSD, Eli Lilly, Pfizer, AstraZeneca/MedImmune, Sanofi Genzyme corporation, Sanofi/Prex, Regeneron Pharmaceuticals, Eli Lilly, Mirati Therapeutics, Inc., Janssen pharmaceutical, io biotech, Merck, Novocure, Nuvation, Pfizer, revolution medicine, Roche, Merck, AstraZeneca, Bayer, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Gilead, Mirati; Financial Interests, Personal, Invited Speaker: WebMD, WebMD Oncology/Takeda, MSD Italia, Srl, GrupoPacifico-Secretaria Técnica ICAPEM/AstraZeneca, S. O.S S.r.l, Medscape, ecancer, Ideology, Gilead, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, Global Experts Meeting: AstraZeneca; Financial Interests, Personal, Other, AstraZeneca Spain: Invitation to a lung cancer investigator meeting: AstraZeneca; Financial Interests, Personal, Advisory Board, Advisory Boards: Takeda, Daiichi Sankyo, BeiGene; Financial Interests, Personal, Other, PACIFIC-R Global Scientific Committee: AstraZeneca; Financial Interests, Personal, Other, Steering Committee member and Co-chair at the AstraZeneca Lung Cancer Summit 2019: AstraZeneca; Financial Interests, Personal, Other, MK-3475 KN671 Steering Committee.: MSD; Financial Interests, Personal, Other, Pacific 6 International Coordinating Investigator: AstraZeneca; Financial Interests, Personal, Other, Janssen Scientific Advisory Board and Therapeutic Area Steering Committee Meeting on Lung Cancer: Janssen; Financial Interests, Personal, Expert Testimony: AstraZeneca UK; Financial Interests, Personal, Other, Pfizer Global Lung Cancer Educational Programme - Steering Committee: Pfizer; Financial Interests, Personal, Other, Seattle Genetics Lung Cancer Platform Study: Seattle Genetics; Financial Interests, Personal, Other, GSK Lung Cancer Global Council: GSK; Financial Interests, Personal, Other, PACIFIC-R Scientific Committee: AstraZeneca UK; Financial Interests, Personal, Other, GSK-Garassino-ZEAL Steering Committee 2020–23: GSK; Financial Interests, Personal, Advisory Board, Advisory Board: AbbVie, Abion, Bayer; Financial Interests, Personal, Advisory Board, Advisory boards: Merck, Sanofi, Gilead; Financial Interests, Personal, Invited Speaker, Satellite Symposium: Merck; Financial Interests, Personal, Invited Speaker, Invited speaker: Medscape; Financial Interests, Personal, Advisory Board, Invited speaker: OncoHost; Financial Interests, Personal, Advisory Board, Advisor: Boehringer; Financial Interests, Personal, Invited Speaker, Member of the MK-3475 KN671 Steering Committee (KEYNOTE-671): MSD; Financial Interests, Personal, Invited Speaker, Coordinating investigator for the MK-3475 KEYNOTE 189: MSD; Financial Interests, Personal and Institutional, Invited Speaker, Pacific 6 Steering Committee and International Coordinating Investigator: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Steering Committee ML41118 Roche: Roche; Financial Interests, Institutional, Invited Speaker, TURNING POINT: Bayer; Financial Interests, Institutional, Invited Speaker, A Phase 1: Janssen; Financial Interests, Institutional, Invited Speaker, Array 818-202: Pfizer; Financial Interests, Institutional, Invited Speaker, PAPILLON Study: Janssen; Financial Interests, Institutional, Invited Speaker, Phase II: Celgene Corporation, Spectrum Pharmaceuticals, Merk Serono; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker, Phase 3: Bluprint; Financial Interests, Institutional, Invited Speaker, Phase III: Amgen, GSK Research & Development Ltd., Novartis; Financial Interests, Institutional, Invited Speaker, Phase III - CEACAM5: Sanofi; Financial Interests, Institutional, Invited Speaker, Phase I-JNJ-61186372, a Human Bispecific EGFR and cMet Antibody: Janssen; Financial Interests, Institutional, Invited Speaker, Phase 3 Study RESILIENT: Ipsen Bioscience Inc.; Financial Interests, Institutional, Invited Speaker, Phase II - SAVANNAH: AstraZeneca S.p.A.; Financial Interests, Institutional, Invited Speaker, phase III NEOCOAST: MedImmune LCC; Financial Interests, Institutional, Invited Speaker, Phase II - coast: MedImmune LCC; Financial Interests, Institutional, Invited Speaker, Phase III - ADRIATIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Phase III (CANOPY-1): Novartis; Financial Interests, Institutional, Invited Speaker, Phase 1b: Exelixis Inc.; Financial Interests, Institutional, Invited Speaker, Phase 3-GO40241: Roche; Financial Interests, Institutional, Invited Speaker, Phase III- CASPIAN: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MK3475-091 - PEARLS: Merk; Financial Interests, Institutional, Invited Speaker, Phase III - Roche GO29431: Roche; Financial Interests, Institutional, Invited Speaker, Phase III CA209-017: BMS; Financial Interests, Institutional, Invited Speaker, Phase III - ARCTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Phase III - AURA 3: AstraZeneca AB; Financial Interests, Institutional, Invited Speaker, Phase III CA209-057: BMS; Financial Interests, Institutional, Invited Speaker, OPEL/2014/14/067: Otsuka Pharmaceutical Italy S.r.l.; Financial Interests, Institutional, Invited Speaker, Phase II - VISION: Merck KGaA; Financial Interests, Institutional, Invited Speaker, Phase III MK-3475-715: Incyte Corporation; Financial Interests, Institutional, Invited Speaker, Phase 1/2 (TRIDENT-1): Turning Point Therapeutics, Inc.; Financial Interests, Institutional, Invited Speaker, HERTHENA-Lung01: A Phase 2: Daiichi Sankyo Development Ltd.; Financial Interests, Institutional, Invited Speaker, Phase II ATLANTIC: AstraZeneca S.p.A.; Financial Interests, Institutional, Invited Speaker, Clinical trial: Affimed; Financial Interests, Institutional, Invited Speaker, Clinical trial poziotinib: spectrum; Non-Financial Interests, Personal, Principal Investigator, STYLE Trial: Pfizer; Non-Financial Interests, Personal, Principal Investigator, Studio TYME: Eli Lilly; Non-Financial Interests, Personal, Principal Investigator, People: MSD; Non-Financial Interests, Personal, Principal Investigator, FAME trial: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, POST-ALK: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, Bando finalizzata Mesotelioma: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, TERAVOLT: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, Progetto Timoma: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, APOLLO: Istituto Nazionale dei Tumori; Non-Financial Interests, Personal, Principal Investigator, Beverly: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Personal, Principal Investigator, IND227: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Personal, Principal Investigator, RAMES: GOIRC; Non-Financial Interests, Personal, Principal Investigator, Studio CHANCE: GOIRC; Non-Financial Interests, Personal, Principal Investigator, Creta trial: Sant’Orsola Malpighi - Bologna (Alma Mater Studiorum Università Bologna); Non-Financial Interests, Personal, Principal Investigator, MILES 5: Istituto dei Tumori Pascale - Napoli; Non-Financial Interests, Personal, Principal Investigator, LIPI: GUSTAVE-ROUSSY PARIGI LIPI TRIAL- no profit; Non-Financial Interests, Personal, Principal Investigator: AO Spedali Civili Brescia; Non-Financial Interests, Personal, Principal Investigator, phase III trial: European Thoracic Oncology Platform (ETOP); Non-Financial Interests, Personal, Leadership Role, Honorary President and Founder: Women for Oncology Italy; Non-Financial Interests, Personal, Other, Member of ASCO Scientific Committee (2018–2021): ASCO; Non-Financial Interests, Personal, Leadership Role, Board member: AIOT (Associazione Italiana Oncologia Toracica); Non-Financial Interests, Personal, Member: AIOM, AIOT; Non-Financial Interests, Personal, Member, WCLC annual congress Lung Cancer Track: WCLC; Non-Financial Interests, Personal, Member, Scientific Committee: IPOP (Italian lung cancer charity), TUTOR (Italian thymic malignancies charity); Non-Financial Interests, Personal, Member, Member since 2013–2018: EMA Scientific Advisory Group (SAG); Non-Financial Interests, Personal, Other, Scientific Programme Committee: AACR; Non-Financial Interests, Personal, Leadership Role, previous ESMO National Societies Committee Chair and ESMO Council Member: ESMO; Other, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Other, Personal, Other, Relationships to Disclose Travel, Accommodations, Expenses: Roche, AstraZeneca; Other, Personal, Other, travel and accommodation: Merk. S. Kilickap: Financial Interests, Personal, Other, meetings and/or travel: Sanofi. M. Ozguroglu: Financial Interests, Personal, Advisory Board: Sanofi-Regeneron; Financial Interests, Personal, Other, meetings and/or travel: Regeneron. M. Gumus: Financial Interests, Personal, Other, meetings and/or travel: Regeneron. M. Schenker: Financial Interests, Personal and Institutional, Invited Speaker, Payment for Clinical trials activities: B.M.S., M.S.D., Roche, Merck Serono, Sanofi, Regeneron, AstraZeneca, Pfizer, G.S.K, Novartis, Astellas, Pharma Mar, BeiGene, Clovis Pharmaceutical, AbbVie, Bioven, Mylan, Samsung Pharmaceutical, Eisai, Gilead, Amgen, Daiichi Sankyo. 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, MSD, F. Hoffmann-La Roche AG, Eisai, Takeda; Financial Interests, Personal, Other, Chairperson: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Regeneron Pharmaceuticals, Merck & Co., Inc., AB Science, Astellas, Tessa Therapeutics, Roche, Arcus Bioscience, AstraZeneca, Pfizer, Janssen Research & Development, Mirati Therapeutics, Novartis, Amgen, Boehringer Ingelheim; Non-Financial Interests, Institutional, Product Samples: Eli Lilly, Janssen Pharmaceuticals, Novartis, Pfizer, Taiho; Non-Financial Interests, Personal, Training: MSD, Ipsen, AstraZeneca, Bristol Myers Squibb, Regeneron Pharmaceuticals, Dr Reddy’s, Roche. M. Kaul: Financial Interests, Institutional, Full or part-time Employment, Global safety Lead for cemiplimab: Regeneron Pharmaceuticals; Financial Interests, Institutional, Stocks/Shares: Regeneron Pharmaceuticals. J. Perez: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. H. Magnan: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. J. Pouliot: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. All other authors have declared no conflicts of interest.