Immunotherapy for the prevention of high-risk oral disorders malignant transformation: the IMPEDE trial

BackgroundOral Potentially Malignant Disorders (OPMD) have a non-negligible malignant transformation rate of up to 8%. Loss of heterozygosity (LOH) in critical chromosomal loci has proven to be the most effective marker in defining the risk of transformation and it is found in about 28% of OPMD and may therefore identify patients carrying higher risk. To date, clinical management of OPMD is limited to surgical excision and clinical surveillance, which however do not fully prevent oral cancer development. Immune system has been shown to play a key role in transformation surveillance mechanism and an immunosuppressive imbalance may be responsible for progression to cancer. Given all these considerations, we designed a clinical trial with the aim to prevent OPMD neoplastic transformation and revert the LOH status.MethodsThis is a phase II, open label, single arm, multicentric trial involving Italian referral centres and expected to enrol 80 patients out of a total of 175 screened. Patients who meet all inclusion criteria and test positive for LOH after an incisional biopsy of the OPMD will undergo a short course of immunotherapy with 4 administration of avelumab. After 6months since treatment start, resection of the entire OPMD will be performed and LOH assessment will be repeated. The follow-up for malignant transformation and safety assessment will last 30months from the end of treatment, for a total planned study duration of approximately 5.5years.DiscussionRestoring the activity of immune system through checkpoint inhibitor may play a crucial role against malignant transformation of OPMD by reverting the balance in favour of immune control and preventing cancer occurrence.Trial registrationThis trial was prospectively registered in ClinicalTrials.gov as NCT04504552 on 7th August 2020.

Automated summary

OPMD have a significant risk of malignant transformation, with potential progression to oral cancer. This clinical trial aims to prevent neoplastic transformation of OPMD and revert LOH status by restoring immune system activity through immunotherapy. By using checkpoint inhibitors, the trial seeks to tip the balance in favor of immune control and prevent cancer occurrence.