A phase II open label, single arm study to evaluate the efficacy of pembrolizumab for leukoplakia.
Authors: Porter Ashleigh , Zeh Audrey J. , Ly Thu , Serna Alyssa , Villanueva Arturo , Chai-Ho Wanxing , Messadi Diana , Maie St. John , Wang Marilene , Abemayor Eliot , Cohen Ezra E.W. , Wong Deborah J.L. 
Published: June 2021

TPS10606 Background: The presence of pre-cancerous oral lesions such as leukoplakia or erythroleukoplakia are known risk factors for the development of squamous cell carcinoma of the head and neck (SCCHN), however preventative agents have not yet shown clinical benefit. The risk of malignant transformation varies but has been quoted as high as 36% in some studies. While the primary mode of treatment of these lesions is largely surgical, recurrence rates are high. Pembrolizumab is a potent and selective humanized monoclonal antibody that is designed to directly block the interaction between PD-1 and PD-L1 (as well as PD-L2) that is currently FDA-approved for treatment of SCCHN. We have hypothesized that the treatment of oral premalignant lesions with pembrolizumab would be an effective and well-tolerated strategy to prevent transformation to invasive cancer. Methods: This study is an open-label, phase II study that will accrue 26 patients with leukoplakia, erythroleukoplakia, or proliferative verrucous leukoplakia with documented moderate to severe dysplasia or carcinoma in situ to be treated with pembrolizumab 200mg every 3 weeks for a total of 6 months. Patients must have visible and measurable lesions that will be both photographed and measured in two dimensions at each visit from the start of treatment until 12 months post-enrollment. Biopsies will be required at diagnosis and following the final treatment, with an optional biopsy following cycle 2 and at progression of disease. Major exclusion criteria include patients with mild dysplasia or hyperplasia, prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks of Day 1 of study, or patients with a known additional malignancy that is active. Patients will also be excluded if they have received anti-PD-1, anti-PD-L1 or anti-PD-L2 treatments in the past. The primary objective is clinical response rate at 6 months, and will be quantified as the percentage of patients with a complete response (CR) and partial response (PR) at 6 months. A CR is defined as complete resolution by visual inspection for 4 weeks of more and a PR is defined as 50% or greater reduction of the product of the 2 dimensions of a single lesions or the sum of all lesions. Progressive disease (PD) is defined as unequivocal increase (greater than or equal to 5mm in one dimension and greater than 20% increase) or the development of new lesions. Secondary objectives will include histologic response rate at 6 months, change in clinical impression based on photographs, clinical response rate at 9 and 12 months, and toxicity. Additional exploratory objectives will include PD-L1 expression in leukoplakia lesions as well as p16 expression, presence of tumor infiltrating lymphocytes, and immunohistochemical as well as RNA sequencing gene expression profiling which may allow for the identification of novel biomarkers. Enrollment began in June 2019 and is ongoing. Clinical trial information: NCT03603223 .