Data from A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms

Abstract

<div>AbstractPurpose:<p>Treatment options are limited in patients with metastatic neuroendocrine neoplasms (NEN). We present the results for a phase II trial of combination nivolumab and temozolomide in patients with advanced NEN along with results of immune changes in peripheral blood.</p>Patients and Methods:<p>NCT03728361 is a nonrandomized, phase II study of nivolumab and temozolomide in patients with NEN. The primary endpoint was response rate using RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Immune profiling was performed by mass cytometry to evaluate the effect on peripheral blood immune cell subsets.</p>Results:<p>Among all 28 patients with NEN, the confirmed response rate was 9/28 [32.1%, 95% confidence interval (CI): 15.9–52.4]. Of 11 patients with lung NEN, the response rate was 64% (<i>n</i> = 7); there was a significant difference in responses by primary tumor location (lung vs. others, <i>P</i> = 0.020). The median PFS was 8.8 months (95% CI: 3.9–11.1 months), and median OS was 32.3 months (95% CI: 20.7—not reached months). Exploratory blood immune cell profiling revealed an increase in circulating CD8<sup>+</sup> T cells (27.9% ± 13.4% vs. 31.7% ± 14.6%, <i>P</i> = 0.03) and a decrease in CD4<sup>+</sup> T cells (59.6% ± 13.1% vs. 56.5% ± 13.0%, <i>P</i> = 0.001) after 2 weeks of treatment. LAG-3–expressing total T cells were lower in patients experiencing a partial response (0.18% ± 0.24% vs. 0.83% ± 0.55%, <i>P</i> = 0.028). Myeloid-derived suppressor cell levels increased during the study and did not correlate with response.</p>Conclusions:<p>Combination nivolumab and temozolomide demonstrated promising activity in NEN.</p><p><i><a href="https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-22-3229" target="_blank">See related commentary by Velez and Garon, p. 691</a></i></p></div>