Immune checkpoint inhibitor in high-risk oral potentially malignant disorders (IMPEDE study): An interim analysis on safety.

person Andrea Alberti Medical Oncology Unit, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy info_outline Andrea Alberti, Chiara Romani, Alberto Paderno, Simonetta Battocchio, Laura Ardighieri, Consuelo D'Ambrosio, Raul Pellini, Giorgio Peretti, Maria Cossu Rocca, Mohssen Ansarin, Paolo Boscolo Rizzo, Lorenzo Azzi, Giovanni Lodi, Carlo Gervasoni, Stefania Vecchio, Elena Bardellini, Alessandra Majorana, Cesare Piazza, Fabio Facchetti, Paolo Bossi

Authors person Andrea Alberti Medical Oncology Unit, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy info_outline Andrea Alberti, Chiara Romani, Alberto Paderno, Simonetta Battocchio, Laura Ardighieri, Consuelo D'Ambrosio, Raul Pellini, Giorgio Peretti, Maria Cossu Rocca, Mohssen Ansarin, Paolo Boscolo Rizzo, Lorenzo Azzi, Giovanni Lodi, Carlo Gervasoni, Stefania Vecchio, Elena Bardellini, Alessandra Majorana, Cesare Piazza, Fabio Facchetti, Paolo Bossi Organizations Medical Oncology Unit, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia, ASST Spedali Civili, Brescia, Italy, Angelo Nocivelli Institute of Molecular Medicine, University of Brescia and ASST-Spedali Civili of Brescia, Brescia, Italy, Unit of Otorhinolaryngology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, Italy, Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, ASST-Spedali Civili, Brescia, Italy, Department of Oncology and Hematology, Azienda Ospedaliero Universitaria Policlinico, Modena, Italy, Department of Otolaryngology, Head and Neck Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy, Department of Otorhinolaryngology, Head and Neck Surgery, University of Genoa, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, Medical Oncology Division of Urogenital and Head and Neck Tumors, European Institute of Oncology, Milan, Italy, Department of Otorhinolaryngology and Head and Neck Surgery, European Institute of Oncology, IRCCS, Milan, Italy, Department of Medical, Surgical and Health Sciences, Section of Otolaryngology, University of Trieste, Trieste, Italy, Department of Medicine and Surgery, University of Insubria, Azienda Socio-Sanitaria Territoriale dei Sette Laghi, Varese, Italy, Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, IRCCS Galeazzi Orthopaedic Institute, Milan, Italy, Department of Maxillofacial Surgery, Sant'Anna Hospital, San Fermo Della Battaglia, Como, Italy, Medical Oncology 2, IRCCS San Martino, IST National Cancer Institute, University of Genoa, Genoa, Italy, School of Paediatric Dentistry- Dental Clinic, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, ASST-Spedali Civili of Brescia, Brescia, Italy, Pathology Unit, Department of Molecular and Translational Medicine, University of Brescia, ASST Spedali Civili, Brescia, Brescia, Italy Abstract Disclosures Research Funding Other Foundation Italian association for cancer research (AIRC) Background: Oral Potentially Malignant Disorders (OPMD) represent the most common oral precancerous condition, with a variable risk of malignant transformation. The most effective biomarker in predicting malignant transformation risk is loss of heterozygosity (LOH). Patients (pts) carrying OPMD with LOH at 3p14 and/or 9p21 plus LOH at another locus have an expected 3-year risk of developing oral cancer of 35%. This chromosomal profile is found in about 30% of OPMD. IMPEDE is a phase II, open-label, single-arm trial designed to evaluate the efficacy of PD-L1 inhibitor avelumab in reverting cancer transformation risk in OPMD with LOH. In this analysis, we report the first safety results, while data about treatment activity need longer follow up. Methods: During the screening period, pts undergo OPMD biopsy. If pathological diagnosis of dysplasia is confirmed, LOH valuation is performed and in case of positivity of this biomarker, subjects receive a short course of immunotherapy with avelumab 800 mg every 2 weeks for 4 total administrations. Follow-up after last avelumab dose is performed monthly and adverse event data are collected at every visit. Six months after treatment start, surgery and LOH re-assessment are performed. Results: Between November 2020 and December 2022, 49 pts were screened in 8 Italian centers. Of these, 16 pts (33%) had a LOH and 12 received the treatment (3 males, median age 65.5 years, range 49-81). Nine out of 12 treated patients had a previous oral cancer. After a median follow up of 14 months, 39 adverse events (AE) of any grade were reported, of these 18 were considered as immune related AEs (irAE). The most frequent AEs was grade 1 (G1) oral pain (4/12 pts), managed with local painkillers. Only three G2 irAEs were reported, namely amylase/lipase increase, psoriasis and fever. No grade 3-4 AEs were described, and no patient had to stop immunotherapy because of toxicities. Local excision after immunotherapy was not delayed by any treatment toxicities. Conclusions: This is the first trial with immunotherapy in an enriched population of OPMD selected according to LOH. First results support the feasibility of this approach, showing that immunotherapy with avelumab is safe and does not compromise subsequent local surgery. Clinical trial information: NCT04504552.

Clinical