Abstract
Background: Limited data are available on nivolumab in challenging subgroups with advanced melanoma. We report outcomes of nivolumab after prior ipilimumab in patients who are typically excluded from clinical trials. Patients and methods: In this phase II, single-arm, open-label, multicentre study (CheckMate 172), patients with advanced melanoma who progressed on or after ipilimumab received nivolumab 3 mg/kg, every 2 weeks for up to 2 years. The primary objective was incidence of grade ≥3, treatment-related select adverse events (AEs). Results: At a minimum follow-up of 18 months, grade ≥3 treatment-related select AEs with the most variation across subgroups were diarrhoea and colitis (1.1% [n = 11] and 0.3% [n = 3] for the total population [n = 1008]; 0.6% [n = 1] and 0.6% [n = 1] for patients with an asymptomatic central nervous system [CNS] metastasis [n = 165; 16.4%]; 4.5% [n = 3] and 3.0% [n = 2] for patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 2 [n = 66; 6.5%]; 2.4% [n = 2] and 0% for those who experienced a grade 3/4 immune-related AE [irAE] with prior ipilimumab [n = 84; 8.3%]; and 0% and 0% for autoimmune disease [n = 25; 2.5%], respectively). Median overall survival was 21.4 months in the total population and was 11.6, 2.4, 21.5, and 18.6 months in patients with a CNS metastasis, ECOG PS 2, a grade 3/4 irAE with prior ipilimumab, and autoimmune disease, respectively. Conclusions: In this large, phase II clinical trial of patients with advanced melanoma who progressed on or after ipilimumab, nivolumab demonstrated a safety profile consistent with that of prior clinical trials. ClinicalTrials.gov ID: NCT02156804.
| Original language | English |
|---|---|
| Journal | European Journal of Cancer |
| Volume | 121 |
| Pages (from-to) | 144-153 |
| Number of pages | 10 |
| ISSN | 0959-8049 |
| DOIs | |
| Publication status | Published - 11.2019 |
Funding
This work was supported by Bristol-Myers Squibb (Princeton, NJ, USA). D. Schadendorf has received grants, personal fees, and non-financial support from Bristol-Myers Squibb and Novartis for participation in advisory boards; has received speaker honoraria and patients' fees paid to his institution from Bristol-Myers Squibb and Novartis; has received personal fees and non-financial support from Roche , MSD/Merck , Amgen , Merck-EMD , Pierre Fabre , Philogen , and Incyte for participation in advisory boards; has received speaker honoraria and patients' fees paid to his institution from Roche, MSD/Merck, Amgen, Merck-EMD, Pierre Fabre, Philogen, and Incyte; has received non-financial support and patients' fees paid to his institution from Regeneron; has received speaker's honoraria and personal fees for participation in advisory boards from Sanofi; has received personal fees and non-financial support for participation in advisory boards and patients' fees paid to his institution from 4SC; and has received personal fees from Array and Pfizer for participation in advisory boards. P.A. Ascierto declares a consulting or advisory role for Bristol-Myers Squibb, Roche-Genentech, MSD, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, Genmab, NewLink Genetics, MedImmune, AstraZeneca, Syndax, Sun Pharmaceuticals, Sanofi, Idera, Ultimovacs, Sandoz, and Immunocore; has received research funds from Bristol-Myers Squibb and Array; and has received travel support from MSD. J. Haanen has received grants from Bristol-Myers Squibb, Novartis, MSD, and Neon Therapeutics for research performed at his institution; and has received financial compensation paid to his institution from AstraZeneca, Celsius Therapeutics, Bayer, Bristol-Myers Squibb, MSD, Merck Serono, Pfizer, GSK, Neon Therapeutics, Immunocore, Seattle Genetics, Roche/Genentech, and Gadeta for serving as an advisor. E. Espinosa has received personal fees from Bristol-Myers Squibb for participation in advisory boards. L. Demidov has received grants from Novartis for research performed at his institution; has received personal fees from Novartis, Bristol-Myers Squibb, MSD, and BIOCAD for travel and accommodations during congresses; and has received personal fees from Roche, Bristol-Myers Squibb, and BIOCAD for participation in advisory boards. C. Garbe has received grants and personal fees from Bristol-Myers Squibb, Novartis, Roche, and Sanofi for participation in advisory boards; has also received personal fees from Amgen, MSD, and Pierre Fabre for participation in advisory boards; and has received grants and personal fees from NeraCare and personal fees from Philogen for serving as an advisor. M. Guida has received grants from Bristol-Myers Squibb, MSD, and Novartis for participating in advisory boards. P. Lorigan has received personal fees from Bristol-Myers Squibb and GSK for consulting, lectures, and clinical trials; has received personal fees from Merck and Chugai for consulting and lectures; and has received personal fees from Novartis and Amgen for consulting and clinical trials. V. Chiarion-Sileni has received personal fees from Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre, and Merck Serono for participation in advisory boards. H. Gogas has received grants from Bristol-Myers Squibb, Roche, MSD, and Novartis for research performed at her institution; has received personal fees from Bristol-Myers Squibb, Roche, and Amgen for participation in advisory boards and for travel and accommodations; and has received personal fees from MSD, Novartis, and Pierre Fabre for participation in advisory boards. M. Maio has received patients' fees paid to his institution from Bristol-Myers Squibb, MSD, AstraZeneca, Roche, and Merck; and has received personal fees from MSD, AstraZeneca, Roche, and Merck for participation in advisory boards. M.T. Fierro has received personal fees from Pierre Fabre and Novartis for participation in advisory boards; and has received travel expenses from Bristol-Myers Squibb. C. Hoeller has received personal fees from Amgen, Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre, and Roche for participation in advisory boards and lectures. P. Terheyden has received personal fees for consulting, honoraria for lectures, and travel expenses from Bristol-Myers Squibb and Pierre-Fabre; has received personal fees for consulting and honoraria for lectures from Novartis and Roche; has received personal fees for consulting and travel expenses from Merck Serono; has received personal fees and honoraria for lectures from CureVac; and has received personal fees for consulting from Sanofi. R. Gutzmer has received personal fees and non-financial support from Bristol-Myers Squibb, Roche, Merck Serono, and Pierre Fabre, as well as meeting support and honoraria for lectures and advice; has received grants, personal fees, non-financial support, and honoraria for lectures and advice from Amgen and Novartis; has received personal fees, non-financial support, and honoraria for lectures and advice from Sanofi Regeneron and Almirall Hermal; has received personal fees and honoraria from MSD and Sun Pharmaceuticals for lectures and advice. He has received grants, personal fees and honoraria from Pfizer for lectures and advice; has received personal fees and honoraria from LEO and 4SC for advice; has received personal fees and honoraria from AstraZeneca for lectures; and has received grants from Johnson & Johnson. T.K. Guren has no conflicts of interest to disclose. D. Bafaloukos has received personal fees from Bristol-Myers Squibb, MSD, and Roche for participation in advisory boards. P. Rutkowski has received personal fees and honoraria for lectures and advisory boards from Bristol-Myers Squibb, Novartis, and MSD; has received personal fees and honoraria for lectures from Roche, Pfizer, Eli Lilly, and Pierre Fabre; and has received personal fees and honoraria for advisory boards from Blueprint Medicines. R. Plummer has received personal fees and speaker honoraria from Bristol-Myers Squibb; has received fees paid to her institution for clinical trial delivery from Bristol-Myers Squibb; has received honoraria for advisory boards from Pierre Faber, Genmab, Bayer, Octimet, Clovis Oncology, Novartis, Karus Therapeutics, Biosceptre, Cybrexa, Ellipses, and Sanofi Aventis; has been paid for delivery of educational talks or chairing educational meetings by AstraZeneca, Novartis, Bayer, and Tesaro; and has received funds to support attendance at conferences from Bristol-Myers Squibb and MSD. A. Waterston has received grants for clinical trial support from Bristol-Myers Squibb; has received travel grants from Bristol-Myers Squibb, and personal fees for lectures and for participation in advisory boards; and has received travel grants and personal fees for lectures from Novartis and MSD. M. Kaatz has received grants for study fees from Bristol-Myers Squibb, Novartis, Roche, MSD, Sun Pharmaceutical, and Sanofi, as well as personal fees for participation in advisory boards. M. Mandala has received grants for research from Novartis and Roche; and has received personal fees from Bristol-Myers Squibb, Novartis, Pierre Fabre, and Roche for participation in advisory boards. I. Marquez-Rodas has received personal fees from Bristol-Myers Squibb, MSD, Novartis, Roche, Pierre Fabre, Amgen, AstraZeneca, Incyte, Merck Serono, Regeneron, Sanofi and Bioncotech for participation in advisory boards. E. Muñoz-Couselo has no conflicts of interest to disclose. R. Dummer discloses intermittent, project-focused consulting and/or advisory relationships with Novartis, MSD, Bristol-Myers Squibb, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharmaceutical, and Sanofi outside the submitted work. E. Grigoryeva is an employee of Bristol-Myers Squibb. T.C. Young is an employee of Bristol-Myers Squibb. P. Nathan has received personal fees from Bristol-Myers Squibb for participation in trial steering committees and advisory boards; and has received fees for advisory boards or speaker's bureau from AstraZeneca, Immunocore, Ipsen, Merck, MSD, Novartis, Pfizer, Pierre Fabre, and Roche. We thank the patients and families who made this study possible. We thank the investigators and the clinical study teams who participated in this study. We also acknowledge ONO Pharmaceutical Company, Ltd. (Osaka, Japan) for contributions to nivolumab development. Professional medical writing and editorial assistance were provided by Jennifer DiNieri, PhD, and Cara Hunsberger, MS, at StemScientific, an Ashfield Company, funded by Bristol-Myers Squibb. The authors are fully responsible for all content within this manuscript.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
