Blocking TNF to Potentiate the ICI-dependent Immune Awakening in Melanoma

Status: Recruiting
Location: See location...
Study Type: Observational
SUMMARY

Cutaneous melanoma is a bad prognosis skin cancer, which can be treated with immune checkpoint inhibitors (ICI), such as anti-PD-1 (nivolumab, nivo) and anti-CTLA-4 (ipilimumab, ipi). However, about 50% of patients do not respond or relapse within 3 years post therapy induction, and immune-related adverse events (irAEs), such as colitis, are triggered and can be treated with TNF inhibitor (TNFi; ie, infliximab, inflix). The pharmacodynamic impact of TNFi on the immune and clinical responses remain to be clarified. The investigators previously demonstrated that TNFi enhance the efficacy of ICI in mouse melanoma models. Based on preclinical findings, the investigators implemented two clinical trials in advanced melanoma patients, TICIMEL and MELANFalpha. In TICIMEL, patients are concomitantly treated with TNFi \[certolizumab (certo) or inflix\] and ICI (ipi+nivo). In MELANFalpha, patients are treated with ICI alone. Preliminary results show both tritherapies promote systemic MART-1 specific CD8 T cell responses and that certo but not inflix may improve ICI efficacy and Th1 responses. In mouse melanoma models, TNFi enhance the response to ICI. Investigators' primary objective is to decipher how certolizumab and infliximab influence ICI-dependent anti-tumor immune responses in advanced melanoma patients. The secondary objectives are to analyse the cellular and molecular impact anti-TNF have on ICI-dependent anti-melanoma immune responses and clinical activities (irAEs and efficacy). By combining mouse and human data as well ex vivo functional assays, the investigators will dissect the impact treatments have on anti-melanoma immune responses by flow cytometry and transcriptomic analyses. The investigators expect to clarify (i) the mechanisms by which TNFi enhance ICI efficacy, (ii) identify the best TNFi to be combined with ICI in advanced melanoma patients and (iii) discover TNF-dependent biomarkers of resistance.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Inclusion in TICIMEL clinical trial (NCT03293784),

• Inclusion in MELANFα trial (NCT03348891)

Locations
Other Locations
France
Institut Claudius Regaud
RECRUITING
Toulouse
Contact Information
Primary
Bruno SEGUI, Pr
bruno.segui@inserm.fr
+33 (0)5 82 74 16 21
Time Frame
Start Date: 2023-01-01
Estimated Completion Date: 2026-12-31
Participants
Target number of participants: 100
Related Therapeutic Areas
Sponsors
Leads: Institut Claudius Regaud
Collaborators: Institut National de la Santé Et de la Recherche Médicale, France

This content was sourced from clinicaltrials.gov