Combining Nivolumab and Ipilimumab with Infliximab or Certolizumab in Patients with Advanced Melanoma: First Results of a Phase Ib Clinical Trial.
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Certolizumab Pegol
/ administration & dosage
Female
Follow-Up Studies
Humans
Infliximab
/ administration & dosage
Ipilimumab
/ administration & dosage
Male
Melanoma
/ diagnosis
Middle Aged
Nivolumab
/ administration & dosage
Progression-Free Survival
Skin Neoplasms
/ diagnosis
Treatment Outcome
Tumor Necrosis Factor-alpha
/ antagonists & inhibitors
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
15 02 2021
15 02 2021
Historique:
received:
02
09
2020
revised:
27
10
2020
accepted:
30
11
2020
pubmed:
5
12
2020
medline:
21
1
2022
entrez:
4
12
2020
Statut:
ppublish
Résumé
TNF blockers can be used to manage gastrointestinal inflammatory side effects following nivolumab and/or ipilimumab treatment in patients with advanced melanoma. Our preclinical data showed that anti-TNF could promote the efficacy of immune checkpoint inhibitors. TICIMEL (NTC03293784) is an open-label, two-arm phase Ib clinical trial. Fourteen patients with advanced and/or metastatic melanoma (stage IIIc/IV) were enrolled. Patients were treated with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) combined to infliximab (5 mg/kg, Only one dose-limiting toxicity was observed in the infliximab cohort. The two different combinations were found to be safe. We observed lower treatment-related AEs with infliximab as compared with certolizumab. In the certolizumab cohort, one patient was not evaluable for response. In this cohort, four of eight patients exhibited hepatobiliary disorders and seven of seven evaluable patients achieved objective response including four complete responses (CRs) and three partial responses (PRs). In the infliximab cohort, we observed one CR, two PRs, and three progressive diseases. Signs of activation and maturation of systemic T-cell responses were seen in patients from both cohorts. Our results show that both combinations are safe in human and provide clinical and biological activities. The high response rate in the certolizumab-treated patient cohort deserves further investigations.
Identifiants
pubmed: 33272982
pii: 1078-0432.CCR-20-3449
doi: 10.1158/1078-0432.CCR-20-3449
doi:
Substances chimiques
Ipilimumab
0
TNF protein, human
0
Tumor Necrosis Factor-alpha
0
Nivolumab
31YO63LBSN
Infliximab
B72HH48FLU
Certolizumab Pegol
UMD07X179E
Banques de données
ClinicalTrials.gov
['NCT03293784']
Types de publication
Clinical Trial, Phase I
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1037-1047Informations de copyright
©2020 American Association for Cancer Research.
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