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. Issue 2 (1st February 2023)

• Record Type: Journal Article
• Authors: Ready, Neal E; Audigier-Valette, Clarisse; Goldman, Jonathan W; Felip, Enriqueta; Ciuleanu, Tudor-Eliade; Rosario García Campelo, María; Jao, Kevin; Barlesi, Fabrice; Bordenave, Stéphanie; Rijavec, Erika; Urban, Laszlo; Aucoin, Jean-Sébastien; Zannori, Cristina; Vermaelen, Karim; Arén Frontera, Osvaldo; Curioni Fontecedro, Alessandra; Sánchez-Gastaldo, Amparo; Juan-Vidal, Oscar; Linardou, Helena; Poddubskaya, Elena; Spigel, David R; Ahmed, Samreen; Maio, Michele; Li, Sunney; Chang, Han; Fiore, Joseph; Acevedo, Angelic; Paz-Ares, Luis
• Is Part Of: Journal for immunotherapy of cancer. Volume 11:Issue 2(2023)
• Publication Date: 2023-02-01
• Subjects: Immunotherapy -- Clinical Trials, Phase III as Topic -- Programmed Cell Death 1 Receptor -- CTLA-4 Antigen -- Lung Neoplasms; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1136/jitc-2022-006127
• Languages: English
• ISSNs: 2051-1426

Abstract

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 .