Melanoma is a bad-prognosis skin cancer generally treated with monoclonal antibodies that neutralize immune checkpoints such as anti-CTLA-4 (ipilimumab) or anti-PD-1 (nivolumab). Unfortunately, a significant proportion of patients do not respond to these treatments. CRCT Team 4 showed that neutralization of TNFα, a major inflammatory cytokine, potentiates the response to anti-PD-1 in mouse melanoma models. This work constitutes the scientific rationale for the TICIMEL clinical trial, which aims to assess the safety, tolerance and anti-tumor activity of anti-TNFα molecules (certolizumab or infliximab) in combination with ipilimumab and nivolumab, in patients with advanced melanoma. The first results are promising, with signs of activation and maturation of the immune response, lower side effects in patients treated with infliximab, and, up to now, a better clinical response rate in the cohort treated with certolizumab. Investigations are continuing as part of an expansion cohort.
If promising clinical results are confirmed in the expansion cohort, a phase 2 multicenter clinical trial may be set up. Should we confirm the promising clinical results in the expansion cohort, a phase 2, multicenter clinical trial may be set up including a larger number of patients with melanoma or other types of cancer that can be treated with immunotherapy.
Ultimately, our work could lead to the generalization of this new immunotherapy in patients with melanoma or other types of cancer. The use of anti-TNFs in cancer patients, in combination or not with immunotherapies targeting immune checkpoints, has been the subject of two international patents.
- New method for treating melanoma (WO2015173259A1, US10144772B2, ES2748380T3, EP3142685B1)
- Methods and pharmaceutical composition for the treatment of cancer (US10918737B2)
Discover the published article :
Clin Cancer Res. 2021 Feb 15;27(4):1037-1047.doi: 10.1158/1078-0432.CCR-20-3449. Epub 2020 Dec 3.
Combining Nivolumab and Ipilimumab with Infliximab or Certolizumab in Patients with Advanced Melanoma: First Results of a Phase Ib Clinical Trial
Anne Montfort, Thomas Filleron, Mathieu Virazels, Carine Dufau, Jean Milhès, Cécile Pagès, Pascale Olivier, Maha Ayyoub, Muriel Mounier, Amélie Lusque, Stéphanie Brayer, Jean-Pierre Delord, Nathalie Andrieu-Abadie, Thierry Levade, Céline Colacios, Bruno Ségui, Nicolas Meyer
Key words :
- Anti-TNF,
- Anti-PD-1,
- Anti-CTLA-4,
- melanoma,
- clinical trial
Collaborations and thanks
We thank Bristol-Myers Squibb (BMS) for funding the clinical trial and part of the ancillary study. We thank Fondation ARC pour la recherche sur le cancer, Cancéropôle Grand Sud-Ouest (GSO) and Institut Universitaire du cancer Toulouse-Oncopole (IUCT-O) for funding part of the ancillary study. We thank Fondation Toulouse Cancer Santé (FTCS) and Fondation pour la Recherche Médicale (FRM) for covering salary supports.
Contact :
Redaction of the article : Bruno Ségui et Nicolas Meyer
Team CRCT “MELASPHINX : Ceramide metabolism : from basic mechanism to immunotherapy.”
Mail : bruno.segui@inserm.fr; meyer.n@chu-toulouse.fr
One Picture
Clear signs of efficacy in patients treated with nivolumab, ipilimumab and TNF blockers.
A, Best response in all patients from the certolizumab or infliximab cohort. B, CT-scan images showing examples of target tumour regression in a patient from the certolizumab cohort with lung metastasis (left panels) as well as in a patient from the infliximab cohort with liver metastasis (right panel).
