Abstract 846P
Background
CTLA-4 and PD-1 inhibitors have been shown to improve Progression Free survival (PFS) and Overall Survival (OS) in advanced melanoma patients. TNF, which is produced upon immune checkpoint inhibitors, impedes ICI therapy efficacy in preclinical melanoma and colon cancer models. Indeed, we and others have published preclinical analyses showing that the systematic combination of anti-TNF with anti-PD-1 +/- anti-CTLA-4 may improve tolerability and efficacy of the treatment.We conducted a phase Ib clinical trial in advanced melanoma patients at our institution.
Methods
TICIMEL (NCT03293784) is an open label phase Ib clinical trial in treatment naive advanced melanoma patients with two parallel cohorts: ipilimumab/nivolumab/certolizumab (C cohort) and ipilimumab/nivolumab/infliximab (I cohort). Fourteen patients were included in the safety part of the trial that has already been published and 19 patients were additionally included in the expansion part. The objective of the expansion part was to evaluate safety and to screen for preliminary anti-tumor activity of these combinations. We report the safety and activity results of all patients.
Results
Between January 2018 and November 2021 , 33 patients were included: 13 in the I cohort and 20 in the C cohort. One patient in the I cohort did not receive any treatment and was considered as not evaluable for both safety and activity. At the time of data cut-off, With a median follow-up of 20.2 months, one patient in each cohort remains on treatment and first tumor assessment was pending for 1 patient in the C cohort. Thirteen patients in the C cohort and 4 in the I cohort had drug-related G3/4 adverse events. Drug-related AE were mostly hepatobiliary, gastrointestinal and respiratory disorders. In the C and I cohorts, an objective response was observed in 12 patients (CR: 5; PR: 7) and 6 (CR: 2; PR: 4), respectively.
Conclusions
Our study shows that the systematic co-administration of anti-TNF and ipi+nivo is safe. Our final analysis shows that certo+nivo+ipi may have synergistic pharmacodynamic activities, with a promising response rate.
Clinical trial identification
NCT03293784.
Editorial acknowledgement
the authors thank the patients and their famillies.
Legal entity responsible for the study
The authors.
Funding
BMS laboratories, ARC, Inserm transfert.
Disclosure
N. Meyer: Financial Interests, Personal and Institutional, Funding: BMS, MSD; Financial Interests, Personal, Advisory Board: Pierre Fabre, Sanofi, Sun Pharma, Merck, Novartis. All other authors have declared no conflicts of interest.