RT Journal Article
SR Electronic
T1 Combining Nivolumab and Ipilimumab with Infliximab or Certolizumab in Patients with Advanced Melanoma: First Results of a Phase Ib Clinical Trial
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 1037
OP 1047
DO 10.1158/1078-0432.CCR-20-3449
VO 27
IS 4
A1 Montfort, Anne
A1 Filleron, Thomas
A1 Virazels, Mathieu
A1 Dufau, Carine
A1 Milhès, Jean
A1 Pagès, Cécile
A1 Olivier, Pascale
A1 Ayyoub, Maha
A1 Mounier, Muriel
A1 Lusque, Amélie
A1 Brayer, Stéphanie
A1 Delord, Jean-Pierre
A1 Andrieu-Abadie, Nathalie
A1 Levade, Thierry
A1 Colacios, Céline
A1 Ségui, Bruno
A1 Meyer, Nicolas
YR 2021
UL http://clincancerres.aacrjournals.org/content/27/4/1037.abstract
AB Purpose: TNF blockers can be used to manage gastrointestinal inflammatory side effects following nivolumab and/or ipilimumab treatment in patients with advanced melanoma. Our preclinical data showed that anti-TNF could promote the efficacy of immune checkpoint inhibitors.Patients and Methods: TICIMEL (NTC03293784) is an open-label, two-arm phase Ib clinical trial. Fourteen patients with advanced and/or metastatic melanoma (stage IIIc/IV) were enrolled. Patients were treated with nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) combined to infliximab (5 mg/kg, N = 6) or certolizumab (400/200 mg, N = 8). The primary endpoint was safety and the secondary endpoint was antitumor activity. Adverse events (AEs) were graded according to the NCI Common Terminology Criteria for Adverse Events and response was assessed following RECIST 1.1.Results: Only one dose-limiting toxicity was observed in the infliximab cohort. The two different combinations were found to be safe. We observed lower treatment-related AEs with infliximab as compared with certolizumab. In the certolizumab cohort, one patient was not evaluable for response. In this cohort, four of eight patients exhibited hepatobiliary disorders and seven of seven evaluable patients achieved objective response including four complete responses (CRs) and three partial responses (PRs). In the infliximab cohort, we observed one CR, two PRs, and three progressive diseases. Signs of activation and maturation of systemic T-cell responses were seen in patients from both cohorts.Conclusions: Our results show that both combinations are safe in human and provide clinical and biological activities. The high response rate in the certolizumab-treated patient cohort deserves further investigations.