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

NCT05867004 · Status: RECRUITING · Type: OBSERVATIONAL · Enrollment: 100

Last updated 2025-05-29

No results posted yet for this study

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.

Conditions

Sponsors & Collaborators

  • Institut National de la Santé Et de la Recherche Médicale, France

    collaborator OTHER_GOV

  • Institut Claudius Regaud

    lead OTHER

Principal Investigators

  • Bruno SEGUI, Pr · Cancer Research Center of Toulouse

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2023-01-01
Primary Completion
2025-07-03
Completion
2026-12-31

Countries

  • France

Study Locations

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Entities

Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05867004 on ClinicalTrials.gov