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.