Phase 2 study of ipilimumab, nivolumab, and tocilizumab combined with stereotactic body radiotherapy in patients with refractory pancreatic cancer (TRIPLE-R).
Ipilimumab
Nivolumab
Pancreatic cancer
Stereotactic body radiotherapy
TRIPLE-R
Tocilizumab
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
23
07
2022
revised:
19
11
2022
accepted:
23
11
2022
pubmed:
3
1
2023
medline:
28
1
2023
entrez:
2
1
2023
Statut:
ppublish
Résumé
Interleukin-6 blockade and radiation combined with immunotherapy may modulate the tumour microenvironment to overcome immune resistance. We assessed the efficacy of ipilimumab, nivolumab, and tocilizumab combined with stereotactic body radiotherapy (SBRT) in patients with refractory pancreatic cancer (PC). Patients with PC who had progressive disease (PD) or intolerance to gemcitabine- or fluorouracil-containing regimens were enrolled in Part A of the two-part, single-centre, phase 2 study (NCT04258150). SBRT with 15 Gy was administered on day one of the first cycle. Ipilimumab was administered (1 mg/kg every 6 weeks) for a maximum of two infusions. Nivolumab (6 mg/kg) and tocilizumab (8 mg/kg) were given every four weeks until the PD or unacceptable toxicity, or for up to one year. The primary end-point was the objective response rate, with a threshold of 15%. Twenty-six patients were enrolled and treated between April 17, 2020, and January 25, 2021. The median follow-up time at the time of data cutoff (February 7, 2022) was 4.9 months (interquartile range 2.1-7.7). No responses were observed. Five patients (19%; 95% confidence intervals [CI], 7-39) achieved a stable disease. The median progression-free survival was 1.6 months (95% CI 1.4-1.7), and the median overall survival was 5.3 months (95% CI 2.3-8.0). Overall, 19 (73%) experienced adverse events related to the treatment including two (8%) with grade 3 or higher events. The combination of ipilimumab, nivolumab, tocilizumab, and SBRT in patients with PC did not meet the prespecified criteria for expansion for full accrual.
Sections du résumé
BACKGROUND
Interleukin-6 blockade and radiation combined with immunotherapy may modulate the tumour microenvironment to overcome immune resistance. We assessed the efficacy of ipilimumab, nivolumab, and tocilizumab combined with stereotactic body radiotherapy (SBRT) in patients with refractory pancreatic cancer (PC).
METHODS
Patients with PC who had progressive disease (PD) or intolerance to gemcitabine- or fluorouracil-containing regimens were enrolled in Part A of the two-part, single-centre, phase 2 study (NCT04258150). SBRT with 15 Gy was administered on day one of the first cycle. Ipilimumab was administered (1 mg/kg every 6 weeks) for a maximum of two infusions. Nivolumab (6 mg/kg) and tocilizumab (8 mg/kg) were given every four weeks until the PD or unacceptable toxicity, or for up to one year. The primary end-point was the objective response rate, with a threshold of 15%.
RESULTS
Twenty-six patients were enrolled and treated between April 17, 2020, and January 25, 2021. The median follow-up time at the time of data cutoff (February 7, 2022) was 4.9 months (interquartile range 2.1-7.7). No responses were observed. Five patients (19%; 95% confidence intervals [CI], 7-39) achieved a stable disease. The median progression-free survival was 1.6 months (95% CI 1.4-1.7), and the median overall survival was 5.3 months (95% CI 2.3-8.0). Overall, 19 (73%) experienced adverse events related to the treatment including two (8%) with grade 3 or higher events.
CONCLUSION
The combination of ipilimumab, nivolumab, tocilizumab, and SBRT in patients with PC did not meet the prespecified criteria for expansion for full accrual.
Identifiants
pubmed: 36592507
pii: S0959-8049(22)01786-5
doi: 10.1016/j.ejca.2022.11.035
pii:
doi:
Substances chimiques
Nivolumab
31YO63LBSN
Ipilimumab
0
tocilizumab
I031V2H011
Banques de données
EudraCT
['2019-004438-40']
ClinicalTrials.gov
['NCT04258150']
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
125-133Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.