Authors: Hye Ryun Kim, Chang Gon Kim, June-Young Koh, Min Hee Hong, Hyun Jun Hong, DaHee Kim, Nam Suk Sim, Sun Och Yoon, Gamin Kim, Jung Eun Lee, Wonrak Son, Chang Lee, Kyung Hwan Kim, Jeong Seok Lee, Donggeun Yoo, Chan-Young Ock, Yoon Woo Koh
Published: 2023-06-04
DOI: 10.1200/jco.2023.41.16_suppl.6075
Source: Full article
6075 Background: With the increasing prevalence of head and neck squamous cell carcinoma (HNSCC) associated with human papilloma virus (HPV) infection, effective treatment strategies for HPV-positive HNSCC are urgently needed. Here, we present the results of neoadjuvant checkpoint blockade of pembrolizumab, therapeutic HPV DNA vaccine of GX-188E, and long-acting interleukin-7 of GX-I7 for patients with resectable HPV-16 and/or 18-positive HNSCC. Methods: In this single-arm, phase 2 trial, patients with resectable HPV-16 and/or 18-positive HNSCC were enrolled. Patients were given pembrolizumab 200mg on day 1 and day 22; GX-188E 2mg on day 1, 8, and 22; and GX-I7 1200 ug/kg on day 8 before surgical resection. Major pathologic response (MPR; defined as residual viable tumor of less than or equal to 10%) was primary endpoint with null and alternative hypothesis of MPR rate ≤5% and ≥35%, respectively. Secondary objectives were safety, recurrence, and survival. Results: Of the 11 patients included, all underwent surgical resection after neoadjuvant treatment without delays in surgery or increased surgical complications. MPR was achieved in seven patients (63.6%) and pathologic complete response was achieved in four patients (36.3%), which met the primary endpoint. Single cell RNA sequencing of baseline and post-treatment paired specimens revealed that the proportion of follicular helper T cell cluster, featured with CXCR5 and BCL6 expression, was significantly increased among tumor-infiltrating immune cells, accompanied with the reinvigoration of CD8 T cell cluster toward less exhausted phenotypes, represented with the upregulation of TCF7 and CD28 expression. In addition, artificial intelligence-powered spatial analysis revealed that triple combination significantly increased the density of tumor-infiltrating lymphocytes, completely converting immune-desert and immune-excluded type of tumor to inflamed immune phenotype. Conclusions: Neoadjuvant pembrolizumab, GX-188E, and GX-I7 showed promising activity and manageable safety profile in patients with resectable HPV-16 and/or 18-positive HNSCC. Therapeutic induction of brisk immune responses significantly reshaped the tumor microenvironment and associated with pathologic regression, warranting further investigation of pembrolizumab, GX-188E, and GX-I7 for patients with HPV-positive HNSCC. Clinical trial information: NCT05286060 .