Informations générales (source: ClinicalTrials.gov)
Identification of Individual Histological and Blood Markers in Patients With Recurrent or Metastatic Upper Aerodigestive Tract Squamous Cell Carcinoma in Response to Immunotherapies (iMonitORL)
Interventional
N/A
Fondation Hôpital Saint-Joseph (Voir sur ClinicalTrials)
janvier 2024
juin 2026
25 juin 2025
Epidermoid Carcinoma of the Upper Aerodigestive Tract (CEVADS) is the 6th most common
cancer worldwide. Despite current therapies (radiotherapy, surgery and chemotherapy),
cancers of the Upper Aerodigestive Tract (UAT) have a poor prognosis, with a 10-year
survival rate of no more than 20%.
For recurrent or metastatic CEVADS, the therapeutic arsenal, based for many years on
chemotherapy and anti-EGFR (Epidermal Growth Factor Receptor) agents, has been enriched
by a new therapeutic class: PD-1 inhibitors. For CEVADS, PD-1 inhibitors have been
approved for second-line treatment of nivolumab for over a year, and are now used in
first-line treatment of pembrolizumab.
The results of this therapeutic class in CEVADS are not as spectacular as for melanoma or
bronchial cancer. Indeed, only 20% of patients have a favorable response, compared with
half who experience disease progression. This low proportion of responders can be
explained by tumor heterogeneity within CEVADS and poor patient selection.
The only marker used to select patients is PD-L1 expression detected by
ImmunoHistochemistry (IHC). However, it seems that this marker, described as imperfect,
is still little explored in ENT. It needs to be compared with the expression of other
cell lines in the tumor microenvironment, which could play an important role in
resistance to PD-1 inhibitors.
IHC identifies all macrophages using the CD68 marker, while the CD163 marker is specific
to M2 macrophages.
Other targets in the microenvironment are also being investigated, with the discovery of
a Tertiary Lymphocyte Structure (TLS) in melanoma treated with immunotherapy.
It therefore seems necessary to gain a better understanding of the mechanisms of tumor
progression under immunotherapy in order to develop strategies to optimize response to
treatment. This would enable better selection of patients likely to benefit from
immunotherapy, and open up prospects for therapeutic combinations.
The hypothesis is that macrophages, but also other cells and factors in the CEVADS
microenvironment, play a decisive role in resistance to PD-1 inhibitors. The aim is
therefore to continue these macrophage analyses, extend them to other cells in the
microenvironment and link them to other prognostic factors under investigation.
A prospective study will analyze tumor tissue during treatment with PD-1 inhibitors, in
order to correlate all the factors studied with response or resistance to
immunotherapies.
In addition, the oral microbiota, in the lineage of the intestinal microbiota, has been
shown to be highly stable over time and to play a role in the oncogenesis of certain
cancers, notably CEVADS. Like the intestinal microbiota, it could also represent a
prognostic factor in the response to immunotherapies.
Of all the bacteria in this oral microbiota, one has been shown to play a major role:
Fusobacterium nucleatum (F. nucleatum). However, little is known about the mechanism of
action of intratumoral F. nucleatum on the development of CEVADS. In particular, it is
thought to play a role in local cancer immunity, via macrophages, regulatory T cells
(Tregs) and TLRs. Finally, it appears that specific antimicrobial T-cell responses may
cross-react with tumor antigens, hence the importance of also analyzing the metabolome of
commensal bacteria.The aim of this study was to evaluate the evolution of the presence of
this bacterium in saliva, as well as the specific immune response to F. nucleatum in
patients with CEVADS during immunotherapy treatment.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| AP-HP - Hôpital Bichat | Diane EVRARD, MD | Contact (sur clinicalTrials) | |||
| GH PARIS SITE SAINT JOSEPH | Eric RAYMOND, MD, PhD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Hôpital Saint-Louis - Paris - France | Sandrine FAIVRE, MD, PhD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Patients aged ≥ 18 years
- Patients with histologically confirmed CEVADS involving the oral cavity, oropharynx,
hypopharynx or larynx
- Pre-treated patients with a first recurrence (locoregional or metastatic) who are
candidates for immunotherapy
- Patient affiliated to a health insurance plan
- French-speaking patient
- Patient with free, informed and written consent
- Patients aged ≥ 18 years
- Patients with histologically confirmed CEVADS involving the oral cavity, oropharynx,
hypopharynx or larynx
- Pre-treated patients with a first recurrence (locoregional or metastatic) who are
candidates for immunotherapy
- Patient affiliated to a health insurance plan
- French-speaking patient
- Patient with free, informed and written consent
- Patients with a contraindication to immunotherapy (transplant patients)
- Pregnant or breast-feeding patients
- Patient under guardianship or curatorship
- Patient under court protection
- Patient deprived of liberty