Phase 2 study of ipilimumab, nivolumab, and tocilizumab combined with stereotactic body radiotherapy in patients with refractory pancreatic cancer (TRIPLE-R)

Inna M. Chen*, Marco Donia, Christopher A. Chamberlain, Agnete W.P. Jensen, Arianna Draghi, Susann Theile, Kasper Madsen, Jane P. Hasselby, Anders Toxværd, Estrid Høgdall, Torben Lorentzen, Eva E. Wilken, Poul Geertsen, Inge M. Svane, Julia S. Johansen, Dorte Nielsen

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

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.
OriginalsprogEngelsk
TidsskriftEuropean Journal of Cancer
Vol/bind180
Sider (fra-til)125-133
Antal sider9
ISSN0959-8049
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
This study was supported by grants from the Danish Cancer Society (grant no. R268-A15344 ) and Jørgen Holm and Elisa f. Hansens Mindelegat (Grant No. 20105 ).

Publisher Copyright:
© 2022 The Authors

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