Ignite Creation Date:
2024-05-06 @ 7:36 PM
Last Modification Date:
2024-10-26 @ 3:09 PM
Study NCT ID:
NCT06061705
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-11-28
First Post:
2023-09-11
Brief Title:
Identification of Individual Histological and Blood Markers in Patients With Recurrent or Metastatic Upper Aerodigestive Tract Squamous Cell Carcinoma in Response to Immunotherapies
Sponsor:
Fondation Hôpital Saint-Joseph
Organization:
Fondation Hôpital Saint-Joseph
Study Overview
Official Title:
Identification of Individual Histological and Blood Markers in Patients With Recurrent or Metastatic Upper Aerodigestive Tract Squamous Cell Carcinoma in Response to Immunotherapies
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
iMonitORL
Brief Summary:
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 bacteriaThe 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
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 bacteriaThe 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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None