Immune Checkpoint Inhibitor In High Risk Oral Premalignant Lesions
Status:
Recruiting
Trial end date:
2024-03-31
Target enrollment:
Participant gender:
Summary
This trial is designed as a prospective, multi-centre, open-label, single-arm, phase II
study.
Oral Premalignant Lesions (OPL) may be considered the equilibrium phase of the immunoediting
concept, i.e. a dynamic process between the tumour cells and the immune system including
surveillance by the immune system or tumour progression. Thus, an imbalance in
immunosuppressive microenvironment is a possible key in malignant transformation. In this
regard, the activation of the PD-1/PD-L1 pathway has a central role, witnessed by the
expression of PD-L1 by multiple cell types within the microenvironment of OPL
(tumour-associated macrophages, fibroblasts, lymphocytes) and by the fact that PD-L1
expression in epithelial and subepithelial cells is associated with malignant transformation.
The use of checkpoint inhibitors in this setting seems to be justified by this rationale.
Employing intermediate end-point markers during preventive strategies against OPL may allow
the conduction of smaller trials, able to give insights for designing larger studies and to
better select the population receiving benefit from the treatment. In this regard, the
evaluation of phenotypic changes (reduction in size or in grade of dysplasia) may not be
enough to assess the potential benefit of an intervention. Modulation of molecular markers
may be more precise indicator of oral cancer risk in patients with OPL. Thus, the change in
LOH at critical loci may be considered intermediate end-point biomarkers of prevention as
well as predictors of cancer risk at baseline. Previous experience with anti-EGFR agents
showed the feasibility of such measures in a prevention trial.
Phase:
Phase 2
Details
Lead Sponsor:
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia