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Clinical Trial
. 2023 Feb;11(2):e006127.
doi: 10.1136/jitc-2022-006127.

First-line nivolumab plus ipilimumab for metastatic non-small cell lung cancer, including patients with ECOG performance status 2 and other special populations: CheckMate 817

Neal E Ready  1 , Clarisse Audigier-Valette  2 , Jonathan W Goldman  3 , Enriqueta Felip  4 , Tudor-Eliade Ciuleanu  5   6 , María Rosario García Campelo  7 , Kevin Jao  8 , Fabrice Barlesi  9   10 , Stéphanie Bordenave  11 , Erika Rijavec  12 , Laszlo Urban  13 , Jean-Sébastien Aucoin  14 , Cristina Zannori  15 , Karim Vermaelen  16 , Osvaldo Arén Frontera  17 , Alessandra Curioni Fontecedro  18   19 , Amparo Sánchez-Gastaldo  20 , Oscar Juan-Vidal  21 , Helena Linardou  22 , Elena Poddubskaya  23 , David R Spigel  24 , Samreen Ahmed  25 , Michele Maio  26 , Sunney Li  27 , Han Chang  28 , Joseph Fiore  29 , Angelic Acevedo  29 , Luis Paz-Ares  30
Affiliations
Clinical Trial

First-line nivolumab plus ipilimumab for metastatic non-small cell lung cancer, including patients with ECOG performance status 2 and other special populations: CheckMate 817

Neal E Ready et al. J Immunother Cancer. 2023 Feb.

Abstract

Background: CheckMate 817, a phase 3B study, evaluated flat-dose nivolumab plus weight-based ipilimumab in patients with metastatic non-small cell lung cancer (NSCLC). Here, in this research, we report on first-line treatment in patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (cohort A) and special populations (cohort A1: ECOG PS 2; or ECOG PS 0-1 with untreated brain metastases, renal impairment, hepatic impairment, or controlled HIV infection).

Methods: Cohorts A and A1 received nivolumab 240 mg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks. The primary endpoint was the incidence of grade 3-4 and grade 5 immune-mediated adverse events (IMAEs; adverse events (AEs) deemed potentially immune-related, occurring <100 days of last dose, and treated with immune-modulating medication (except endocrine events)) and treatment-related select AEs (treatment-related AEs with potential immunological etiology requiring frequent monitoring/intervention, reported between first dose and 30 days after the last dose) in cohort A; efficacy endpoints were secondary/exploratory. In cohort A1, safety/efficacy assessment was exploratory.

Results: The most common grade 3-4 IMAEs were pneumonitis (5.1%), diarrhea/colitis (4.9%), and hepatitis (4.6%) in cohort A (N=391) and diarrhea/colitis (3.5%), hepatitis (3.5%), and rash (3.0%) in cohort A1 (N=198). The most common grade 3-4 treatment-related select AEs were hepatic (5.9%), gastrointestinal (4.9%), and pulmonary (4.6%) events in cohort A and gastrointestinal (4.0%), skin (3.5%), and endocrine (3.0%) events in cohort A1. No grade 5 IMAEs or treatment-related select AEs occurred. Treatment-related deaths occurred in 4 (1.0%) and 3 (1.5%) patients in cohorts A and A1, respectively. Three-year overall survival (OS) rates were 33.7% and 20.5%, respectively.

Conclusions: Flat-dose nivolumab plus weight-based ipilimumab was associated with manageable safety and durable efficacy in cohort A, consistent with data from phase 3 metastatic NSCLC studies. Special populations of cohort A1 including patients with ECOG PS 2 or ECOG PS 0-1 with untreated brain metastases had manageable treatment-related toxicity and clinically meaningful 3-year OS rate.

Trial registration number: NCT02869789.

Keywords: CTLA-4 Antigen; Clinical Trials, Phase III as Topic; Immunotherapy; Lung Neoplasms; Programmed Cell Death 1 Receptor.

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Conflict of interest statement

Competing interests: NER reports receiving consulting fees from AstraZeneca, Bristol Myers Squibb, Genentech, Jazz, Lilly, Merck, Regeneron and Roche; and other fees (honoraria) from Bristol Myers Squibb. CA-V reports interests (clinical trials, as principal investigator) with AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, MSD, Novartis, Roche, and Sanofi; other fees (consultant/advisor) from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, FoundationOne, GlaxoSmithKline, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, and Takeda; and, as speaker (conferences and invitations) for AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Novartis, Pfizer, and Roche. JWG reports receiving grants/research support from Advaxis, AstraZeneca, Bristol Myers Squibb, Genentech and Merck; and other fees (consultant/advisor) from AstraZeneca, Bristol Myers Squibb, and Genentech. EF reports receiving grants/research support for the institution from Merck; other fees (consultant/advisor) from Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Medical Trends, Merck Serono, Merck Sharp & Dohme, Peptomyc, Pfizer, Puma Biotechnology, Regeneron, Sanofi and Takeda for Advisory Board and Syneos Health for Data Safety and Monitoring; other fees (honoraria) from Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medscape, Merck Serono, Merck Sharp & Dohme, Peervoice, Pfizer, Springer and Touch Medical; and other fees (personal) from Grifols as an independent member of the board. T-EC reports personal fees from Bristol Myers Squibb, during the conduct of the study; personal fees from Amgen, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, Genzyme, Ipsen, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi and Servier; and personal fees from Bristol Myers Squibb, outside the submitted work. MRGC reports receiving consulting fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and Takeda; other fees (honoraria) from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and Takeda; and support for attending meetings for AstraZeneca, Bristol Myers Squibb, Lilly, MSD, Pfizer and Roche. KJ reports receiving consulting fees from Amgen and Novartis; and other fees (honoraria) from AstraZeneca, Bristol Myers Squibb, Janssen, Merck, Pfizer and Takeda. FB reports personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, Hoffmann-La Roche Ltd, Novartis, Merck, MSD, Pierre Fabre, Pfizer and Takeda. SB reports no conflicts of interest. ER reports receiving other fees (honoraria) from Bristol Myers Squibb. LU reports receiving other fees (scholarship) for coursework in Molecular Oncology at the Institute of Bioscience Madrid. J-SA reports receiving grants/research support for the institution from Bristol Myers Squibb, Merck and Roche; other fees (honoraria) from AstraZeneca, Novartis, Pfizer and Sanofi; and participation on Data Safety Monitoring Board or Advisory Board for AstraZeneca, Bristol Myers Squibb, Merck, Novartis, Pfizer and Roche. CZ reports no conflicts of interest. KV reports receiving grants/research support from Bristol Myers Squibb; other fees (honoraria) from Bristol Myers Squibb; support for attending meetings for AstraZeneca, Bristol Myers Squibb and Merck; patents planned/issued/pending on behalf of Ghent University; and participation on Data Safety Monitoring Board or Advisory Board for Amgen, AstraZeneca, Bristol Myers Squibb and Merck. OAF reports receiving other fees (honoraria) from Bristol Myers Squibb of Chile. ACF reports receiving fees (honoraria) from MSD; and participation on Data Safety Monitoring Board or Advisory Board for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Janssen-Cilag, MSD, Pfizer, Roche, and Takeda. AS-G reports no conflicts of interest. OJ-V reports receiving other fees (honoraria) from AstraZeneca, Bristol Myers Squibb, Lilly, MSD, Roche and Takeda; and participation on Data Safety Monitoring Board or Advisory Board for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, MSD and Takeda. HL reports receiving personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Novartis, Pfizer and Roche. EP reports no conflicts of interest. DRS reports all support for present manuscript from Bristol Myers Squibb; receiving grants/research support from Aeglea Biotherapeutics, Agios, Apollomics, Arcus Biosciences, Arrys Therapeutics, Astellas Pharma, AstraZeneca, Bayer, BeiGene, BIND Therapeutics, BioNTech RNA Pharmaceuticals, Blueprint Medicine, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Celgene, Celldex Therapeutics, Clovis, Cyteir Therapeutics, Daiichi Sankyo, Denovo Biopharma, Eisai, Elevation Oncology, EMD Serono, Evelo Biosciences, G1 Therapeutics, Genentech/Roche, GlaxoSmithKline, GRAIL, Hutchison MediPharma, ImClone Systems, Incyte, Ipsen, Janssen, Kronos Bio, Lilly, Loxo, MacroGenics, MedImmune, Merck, Molecular Template, Nektar, Neon, Novartis, Novocure, Oncologie, Pfizer, PTC Therapeutics, PureTech Health, Razor Genomics, Repare Therapeutics, Rgenix, Takeda, Tarveda, Tesaro, Tizona Therapeutics, UT Southwestern, and Verastem; and other fees (consultant/advisor) from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Curio Science, EMD Serono, Evidera, Exelixis, Genentech/Roche, GlaxoSmithKline, Intellisphere, Ipsen, Janssen, Jazz Pharmaceuticals, Lilly, Mirati Therapeutics, Molecular Templates, Novartis, Novocure, Pfizer, Puma Biotechnology, Regeneron and Sanofi-Aventis. SA reports receiving other fees (consultant/advisor) from Bristol Myers Squibb. MM reports other fees (honoraria) from Bristol Myers Squibb, MSD and Merck Serono; support for attending meetings for Alfasigma, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Incyte, Merck, MSD, Pierre Fabre, Roche, Sanofi, and Sciclone; participation on Data Safety Monitoring Board or Advisory Board for Alfasigma, Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Incyte, Merck, Pierre Fabre, Roche, Sanofi, and Sciclone; and has stock in Epigen Therapeutics and Theravance. SL is a Bristol Myers Squibb employee and has stock in Bristol Myers Squibb. HC is a Bristol Myers Squibb employee and has stock in Bristol Myers Squibb. JF is a Bristol Myers Squibb employee and has stock in Bristol Myers Squibb. AA is a Bristol Myers Squibb employee and has stock in Bristol Myers Squibb. LP-A reports receiving grants/research support for the institution from AstraZeneca, Bristol Myers Squibb, MSD and Pfizer; other fees (consultant/advisor) from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, GlaxoSmithKline, Ipsen, Janssen, Lilly, Merck, Mirati, MSD, Novartis, Pfizer, Pharmamar, Roche, Sanofi, Servier and Takeda; other fees (honoraria) from AstraZeneca, Janssen, Merck and Mirati; and other (leadership/fiduciary) from Altum Sequency and Genomica.

Figures

Figure 1
Figure 1
Cumulative time to onset of immune-mediated adverse events (IMAEs) (A), cumulative time to resolution of IMAEs (B), and IMAEs over time (C) in cohort A.
Figure 2
Figure 2
Overall survival (OS) and progression-free survival (PFS) in cohort A. (A) OS and (B) PFS, overall and by tumor programmed death ligand 1 (PD-L1) expression, and (C) OS by tumor histology.
Figure 3
Figure 3
Cumulative time to onset of immune-mediated adverse events (IMAEs) (A), cumulative time to resolution of IMAEs (B), and IMAEs over time (C) in cohort A1.
Figure 4
Figure 4
Overall survival (OS) and progression-free survival (PFS) in cohort A1. (A) OS and (B) PFS, overall and by tumor programmed death ligand 1 (PD-L1) expression, (C) OS and (D) PFS, overall and in patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 and untreated brain metastases. *Asymptomatic, untreated.
See this image and copyright information in PMC

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