2545 - 5-year survival outcomes of the CheckMate 067 phase 3 trial of nivolumab plus ipilimumab (NIVO+IPI) combination therapy in advanced melanoma

Background

Results from CheckMate 067 have shown significant improvements in objective response, progression-free survival (PFS), and overall survival (OS) with NIVO+IPI and NIVO alone vs IPI in patients with advanced treatment-naive melanoma. Here we present 5-year outcomes from the study.

Methods

Eligible patients with previously untreated stage III or IV melanoma (N = 945) were randomly assigned 1:1:1 and stratified by programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. Patients received NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W followed by NIVO 3 mg/kg Q2W (n = 314), NIVO 3 mg/kg Q2W + placebo (n = 316), or IPI 3 mg/kg Q3W for 4 doses + placebo (n = 315) until progression or unacceptable toxicity. Co-primary endpoints were OS and PFS; the study was not powered to compare the NIVO-containing groups. Descriptive analyses were performed to evaluate efficacy between NIVO+IPI and NIVO, treatment-free status, and health-related quality of life (HRQoL).

Results

With a minimum follow-up of 60 months, the NIVO-containing arms continued to show improved OS, PFS, and response vs IPI (table). In addition, descriptive analyses showed longer OS with NIVO+IPI (median OS, > 60.0 mo [not reached]) than with NIVO alone (median OS, 36.9 mo), as well as a higher proportion of patients alive and treatment-free with the combination. No sustained deterioration of HRQoL (EQ-5D-3L utility index) was observed during treatment or following treatment discontinuation with NIVO or NIVO+IPI.Table:

LBA68_PR

NR, not reached.

Although a median was reported at the previous analysis, that estimate was immature and greater than the minimum study follow-up.

> 60.0 mo.

Conclusions

This 5-year analysis represents the longest phase III follow-up for checkpoint inhibitor combination therapy and demonstrates long-term survival with both NIVO-containing arms vs IPI. In descriptive analyses, NIVO+IPI was associated with improved survival and a higher likelihood of being alive and treatment-free compared with NIVO alone, both without loss of QoL.

Clinical trial identification

NCT01844505.

Editorial acknowledgement

Writing and editorial assistance was provided by Melissa Kirk, PhD, and Michele Salernitano of StemScientific, an Ashfield Company.

Legal entity responsible for the study

Bristol-Myers Squibb.

Funding

Bristol-Myers Squibb.

Disclosure

J.M.G. Larkin: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Achilles; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boston Biomedical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): BMS; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: EUSA Pharma; Honoraria (self), Advisory / Consultancy: GSK; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy: Imugene; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy: iOnctura; Honoraria (self), Advisory / Consultancy: Kymab; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Nektar; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self), Advisory / Consultancy: Secarna; Research grant / Funding (self): Aveo; Research grant / Funding (self): Covance; Honoraria (self), Advisory / Consultancy: Vitaccess. V. Chiarion-Sileni: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck-Serono; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Incyte. R. Gonzalez: Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): Genentech/Roche; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): GSK; Honoraria (self), Research grant / Funding (self): Array; Honoraria (self), Research grant / Funding (self): Amgen; Honoraria (self), Research grant / Funding (self): Incyte; Honoraria (self), Research grant / Funding (self): NewLink Genetics; Research grant / Funding (self): Merck; Research grant / Funding (self): Takeda; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Checkmate Pharmaceuticals; Research grant / Funding (self): Tesaro; Research grant / Funding (self): Syndax; Research grant / Funding (self): Nektar. J.J. Grob: Travel / Accommodation / Expenses: Bristol-Myers Squibb; Travel / Accommodation / Expenses: MSD; Travel / Accommodation / Expenses: Roche/Genentech; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: AMGEN; Travel / Accommodation / Expenses: Pierre Fabre; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Sun Pharma. P. Rutkowski: Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pierre Fabre; Honoraria (self): Eli Lilly; Honoraria (self): Pfizer; Honoraria (self): Blueprint Medicines . C. Lao: Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Genentech; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Dynavax; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Immunocore. D. Schadendorf: Honoraria (self): Roche/Genentech; Honoraria (self): Merck Serono; Honoraria (self): Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Novartis, Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck Sharp & Dohme; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Immunocore, Philogen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Incyte, Regeneron; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: 4SC, Mologen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Mologen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Sanofi/Regeneron; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Sysmex; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Grünenthal Group; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Agenus; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Array; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: BioPharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: LEO Pharma. J. Wagstaff: Honoraria (self): Bristol-Myers Squib . R. Dummer: Advisory / Consultancy: Novartis; Advisory / Consultancy: MSD; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Roche; Advisory / Consultancy: Amgen; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Sun Pharma; Advisory / Consultancy: Sanofi; Honoraria (self): Amgen; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Pierre Fabre; Honoraria (self): Roche; Honoraria (self): Sun Pharma; Honoraria (self): Takeda; Honoraria (self): Sanofi. P.F. Ferrucci: Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pierre Fabre. M. Smylie: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck; Honoraria (self): Sanofi Genzyme; Honoraria (self): Novartis. D. Hogg: Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): EMD Sereno; Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): Merck. I. Marquez-Rodas: Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self), Research grant / Funding (self): BIONCOTECH; Honoraria (self), Research grant / Funding (self): AMGEN; Honoraria (self), Research grant / Funding (self): Incyte; Honoraria (self): Sanofi ; Honoraria (self): Regeneron. J.B.A.G. Haanen: Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Novartis; Research grant / Funding (self): MSD; Research grant / Funding (self): Neon Therapeutics . J. Rizzo: Honoraria (self), Full / Part-time employment: Bristol-Myers Squibb. A. Balogh: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. F..S. Hodi: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self): Merck, EMD Serono, Takeda, Surface, ; Honoraria (self): Genentech/Roche, Compass Therapeutics,; Honoraria (self): Apricity, Bayer, Aduro, Partners Therapeutics; Honoraria (self): Sanofi, Pfizer, Pionyr, Verastem; Honoraria (self): Rheos, Kairos, Bicara; Honoraria (self), Research grant / Funding (self): Novartis; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Torque, 7 Hills Pharma, Psioxus Therapeutics ; Licensing / Royalties: patent Methods for Treating MICA-Related Disorders (#20100111973) with royalties paid; a patent Tumor Antigens and Uses Thereof (#7250291) issued; a patent Angiopoiten-2 Biomarkers Predictive of Anti-Immune Checkpoint Response (#20170248603) pending; a . J. Wolchok: Patent information: Xenogeneic DNA Vaccines; Alphavirus Replicon Particles Expressing TRP2; Myeloid-derived Suppressor cell (MDSC) assay; Newcastle Disease Viruses for Cancer Therapy; Genomic Signature to Identify Responders to Ipilimumab in Melanoma; Engineered Vaccinia Viruses for Cancer Immunotherapy; Anti-CD40 agonist mAb fused to Monophosphoryl Lipid A (MPL) for cancer therapy; CAR+ T cells targeting differentiation antigens as means to treat cancer; Anti-PD1 Antibody; Anti-CTLA4 antibodies; Anti-GITR antibodies and methods of use thereof; Honoraria (self), Research grant / Funding (self): Bristol-Myers Squibb ; Honoraria (self): Advaxis, Elucida, Amgen, Eli Lilly; Honoraria (self): Apricity, F Star, Array BioPharma, Imvaq; Honoraria (self): Ascentage, Janssen, Astellas, Kleo; Honoraria (self): Bayer, Merck, Adaptive Biotech, Neon Therapeutics; Honoraria (self): Beigene, ONO, Celgene, Polaris Pharma; Honoraria (self): Chugai, Polynoma, PsiOxus, Puretech; Honoraria (self): Recepta, Sellas Life Sciences; Honoraria (self): Serametrix, Surface, Syndax; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Potenza Therapeutics, Tizona Pharma; Honoraria (self), Research grant / Funding (self): Genentech, MedImmune; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Trieza, Linneaus. All other authors have declared no conflicts of interest.