Neoadjuvant Anti-OX40 May Prevent Disease Recurrence And Increase Tumor Immunity In Patients With Resectable HNSCC
R. Bryan Bell, MD (Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR, USA) discussed phase 1b clinical trial (NCT02274155) results investigating efficacy of anti-OX40 (MEDI6469) in the neoadjuvant setting for HNSCC resection candidates.
In all, 17 patients (resectable stage III-IVA HNSCC, 11 = HPV-, 6 = HPV+) received three anti-OX40 doses (0.4mg/kg) daily on day 0, 2, and 4 of the study, and then underwent resection between 2 days – 2 weeks after the last infusion.
In all, no surgical delays or grade 3/4 AEs were observed in patients treated with anti-OX40. At median follow-up (24 mos), 12/17 patients were disease-free. One patient experienced local disease recurrence (HPV-) and four patients had distant disease (3 = HPV-, 1 = HPV+). One death occurred in a patient with recurrent disease 3-months post-treatment.
Increased abundance of Ki67+CD38+ICOS+CD4+ and CD8+ memory T cells were observed in the tumor microenvironment and peripheral blood of four patients post-anti-OX40 treatment via flow cytometry and multiplex immunohistochemistry. Differential expression of genes related to MHC-1 mediated antigen processing was noted between responders and non-responders via RNA sequencing. Additionally, all responders had increased genes correlating with CD39+CD103+CD8+ T cell abundance.
Overall, this data suggests that anti-OX40 treatment is safe in the neoadjuvant setting in patients with resectable HNSCC and that this agent can promote T cell activation and abundance within the tumor microenvironment.