Urelumab, an anti-CD137 agonist antibody, plus nivolumab and a GVAX vaccine, showed some preliminary activity as a neoadjuvant therapy for resected pancreatic cancer, though further studies are needed to determine clinical benefit, according to preliminary results of a study presented at the virtual Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020).
“Most pancreatic cancer will not respond to immune checkpoint inhibitors [ICIs] as a single agent, so we have been wondering if we can convert the pancreatic cancer tumor microenvironment from a cold one to a hot one,” Lei Zheng, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and presenter of the study, said. The purpose of this study was to determine if GVAX could prime the tumor microenvironment to be more responsive to ICIs.
A neoadjuvant trial was designed to evaluate the GVAX vaccine with or without nivolumab among patients with resectable pancreatic cancer. The present analysis is of data from an additional treatment arm that was added to evaluate GVAX plus nivolumab and urelumab.
The 10 evaluable patients who underwent an R0/R1 resection for pancreatic cancer were treated 2 weeks prior to surgery and then 6 to 10 weeks after surgery with GVAX plus nivolumab and urelumab. The primary endpoint was change in tumor-infiltrating CD137-positive CD8-positive T cells. Secondary endpoints included safety, overall survival, disease-free survival, and other immune parameters.
There were 3 patients who achieved a grade 2 pathologic response, and 9 patients were disease-free after a median follow-up of 12 months.
A preliminary analysis of tumor-infiltrating cells using single-cell RNA sequencing demonstrated an initial shift from CD8 expression to expression of both CD8 and EMOES exhaustion markers, which then shifted to CD8 and granzyme B expression followed by granzyme B and PD-1 expression, after triple combination treatment, Dr Zheng said. Expansion of T-cell receptor clones also occurred, particularly among patients treated with the triple combination therapy.
The most common adverse event (AE) associated with urelumab was nausea. One patient each developed arthritis, elevated liver function enzymes, and rash. There were no delays in time to surgery due to AEs.
Dr Zheng concluded in his abstract that these results suggest that “anti-CD137 agonist-based combinations warrant further investigation.”
Disclosure: The presenting author reported financial ties with various pharmaceutical companies. For a full list of disclosures, please refer to the presentation slides.
Zheng L, Judkins C, Hoare J, et al. Urelumab (anti-CD137 agonist) in combination with vaccine and nivolumab treatments is safe and associated with pathologic response as neoadjuvant and adjuvant therapy for resectable pancreatic cancer. Presented at: Society for Immunotherapy of Cancer 35th Anniversary Annual Meeting & Preconference Programs (SITC 2020); November 11-14, 2020. Abstract 812. J Immunother Cancer. 2020;8(Suppl 3):A656–A959.
This article originally appeared on Cancer Therapy Advisor