122MO - Cemiplimab (cemi) + platinum doublet chemotherapy (chemo) + ipilimumab (ipi) for first-line treatment of advanced non-small cell lung cancer (NSCLC): EMPOWER-Lung 3 part I

Background

Cemi (anti-PD-1) used as monotherapy has been shown to improve overall survival (OS) vs chemo in patients (pts) with advanced NSCLC, no EGFR, ALK or ROS1 aberrations, and PD-L1 expression in ≥50% of tumor cells. Since the benefit of PD-(L)1 blockade decreases with decreased PD-L1 expression, combination therapies are required for tumors with low PD-L1. Both chemotherapy and anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) have been shown to augment the effects of anti–PD-1 in pts with advanced NSCLC. The addition of a reduced course of chemo and CTLA-4 to anti-PD1 could provide an additional benefit in pts with PD-L1 expression <50%.

Methods

In EMPOWER-Lung 3 part 1, 323 pts with PD-L1 expression of <50% were randomized (1:1:1) to: standard platinum-based doublet chemo for 4 cycles (StC), cemi 350 mg once every 3 weeks (Q3W) for up to 108 weeks + standard chemo, or cemi 350 mg Q3W for up to 108 weeks + reduced chemo for 2 cycles + ipi 50 mg Q6W for up to 4 cycles (CIC). The primary endpoint was OS. Secondary endpoints included progression free survival (PFS), objective response rate (ORR), patient-reported outcomes, and safety. Part 1 was stopped early due to reprioritization to standard chemo+cemi for NSCLC pts regardless of PD-L1 expression and only descriptive statistical analyses were done.

Results

49% of pts in each group had <1% expression of PD-L1. At a median (med) follow-up of 35.5 months (m), med OS was 20.1m (13.7, 28.3) for CIC pts (N=109) vs 13.9 (10.0, 17.7) for StC pts (N=106), with a hazard ratio (HR) of 0.615 (95% confidence interval, 0.441, 0.857). Med PFS was 6.4m vs 6.3m with HR of 0.813 (0.596, 1.108). ORR was 35.8% and 28.3% for CIC and StC, respectively. Med duration of response was 15.9m vs 6.3m. Safety profile was generally consistent with the known safety profile for cemi, chemo, and ipi. Grade ≥3 treatment emergent adverse events (TEAEs) were observed in 43.1% of CIC pts and 42.7% of StC pts, TEAEs resulting in discontinuation of study treatment or death observed in 4.6% vs 0%, and in 4.6% vs 4.9%, of CIC and StC pts respectively.

Conclusions

In this descriptive analysis, the addition of cemi and ipi to a reduced course of chemo led to a meaningful OS benefit in pts with PD-L1 <50%.

Clinical trial identification

NCT03409614.

Editorial acknowledgement

Medical writing support was provided by Osnat Ben-Shahar PhD of Regeneron Pharmaceuticals, Inc.

Legal entity responsible for the study

Regeneron Pharmaceuticals, Inc. and Sanofi.

Funding

Regeneron Pharmaceuticals, Inc. and Sanofi.

Disclosure

K.D. Penkov: Financial Interests, Personal, Advisory Board: Nektar terapeutics; Financial Interests, Personal and Institutional, Invited Speaker: AbbVie, AstraZeneca, Pfizer, Jounce Terapeutics, Polyphor, GSK, Mabscale, Biocad, Sanofi, Novartis, Regenegon pharmaciutical. E. Kalinka: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, AstraZeneca, Roche, Gilead; Financial Interests, Personal, Writing Engagements: Bristol Myers Squibb, AstraZeneca, Nektar; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, AstraZeneca, Gilead; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb, MSD, AstraZeneca, Roche, Gilead, Nektar. C. Gessner: Financial Interests, Personal, Other: GlaxoSmithKline, Pfizer, AstraZeneca, Roche, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Berlin-Chemie, Chiesi , Boehringer Ingelheim, Sanofi; Financial Interests, Personal, Advisory Board: GlaxoSmithKline , Pfizer, AstraZeneca, Roche, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme , Berlin-Chemie, Chiesi, Boehringer Ingelheim, Sanofi. R. Passalacqua: Financial Interests, Institutional, Research Grant: Amgen, Pierre-Fabre; Financial Interests, Personal, Advisory Board: Amgen, Pierre-Fabre; Financial Interests, Personal, Other: Astellas, Bayer, BMS, Ipsen, Janssen, Novartis, Sanofi-Aventis , Roche, MSD, Regeneron. M.C. Garassino: Financial Interests, Personal, Advisory Board: Eli Lilly, SeaGen International GmbH, Eli Lilly, Daiichi Sankyo, Incyte, GlaxoSmithKline, 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, Astrazenca/MedImmune, Sanofi Genzyme corporation, Sanofi / Prex, Regeneron Pharmaceuticals, Eli Lilly, Mirati Therapeutics, Inc.; Financial Interests, Personal, Invited Speaker: WebMD, WebMD Oncology/Takeda, MSD, MSD Italia, Srl, GrupoPacifico-Secretaria Técnica ICAPEM/AstraZeneca, S.O.S S.r.l, Medscape, ecancer; 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 Board Nazionale Brigatinib: Takeda; 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, Jannesen 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, 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, GlaxoSmithkline Research & Develpoment 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.; 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, Leadership Role, President and Founder: Women for Oncology Italy; 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, 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: EMA Scientific Advisory Group (SAG); Non-Financial Interests, Personal, Other, Scientific Programme Committee: AACR; Non-Financial Interests, Personal, Leadership Role, 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. S. Li: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. J. Pouliot, K. McGuire, R.G. Quek, M. Kaul, G. Gullo: Financial Interests, Personal, Full or part-time Employment: Regeneron; Financial Interests, Personal, Stocks/Shares: Regeneron. P. Rietschel: Financial Interests, Personal, Stocks/Shares: Regeneron; Financial Interests, Personal, Full or part-time Employment: Regeneron. All other authors have declared no conflicts of interest.