Utomilumab in Patients With Immune Checkpoint Inhibitor-Refractory Melanoma and Non-Small-Cell Lung Cancer
- Author(s)
- Hong, DS; Gopal, AK; Shoushtari, AN; Patel, SP; He, AR; Doi, T; Ramalingam, SS; Patnaik, A; Sandhu, S; Chen, Y; Davis, CB; Fisher, TS; Huang, B; Fly, KD; Ribas, A;
- Journal Title
- Frontiers in Immunology
- Publication Type
- Research article
- Abstract
- SECTION HEAD: Clinical/translational cancer immunotherapy. BACKGROUND: The goal of this study was to estimate the objective response rate for utomilumab in adults with immune checkpoint inhibitor (ICI)-refractory melanoma and non-small-cell lung cancer (NSCLC). METHODS: Utomilumab was dosed intravenously every 4 weeks (Q4W) and adverse events (AEs) monitored. Tumor responses by RECIST1.1 were assessed by baseline and on-treatment scans. Tumor biopsies were collected for detection of programmed cell death ligand 1, CD8, 4-1BB, perforin, and granzyme B, and gene expression analyzed by next-generation sequencing. CD8+ T cells from healthy donors were stimulated with anti-CD3 +/- utomilumab and compared with control. RESULTS: Patients with melanoma (n=43) and NSCLC (n=20) received utomilumab 0.24 mg/kg (n=36), 1.2 mg/kg (n=26), or 10 mg/kg (n=1). Treatment-emergent AEs (TEAEs) occurred in 55 (87.3%) patients and serious TEAEs in 18 (28.6%). Five (7.9%) patients discontinued owing to TEAEs. Thirty-two (50.8%) patients experienced treatment-related AEs, mostly grade 1-2. Objective response rate: 2.3% in patients with melanoma; no confirmed responses for patients with NSCLC. Ten patients each with melanoma (23.3%) or NSCLC (50%) had stable disease; respective median (95% confidence interval, CI) progression-free survival was 1.8 (1.7-1.9) and 3.6 (1.6-6.5) months. Utomilumab exposure increased with dose. The incidences of antidrug and neutralizing antibodies were 46.3% and 19.4%, respectively. Efficacy was associated with immune-active tumor microenvironments, and pharmacodynamic activity appeared to be blunted at higher doses. CONCLUSIONS: Utomilumab was well tolerated, but antitumor activity was low in patients who previously progressed on ICIs. The potential of 4-1BB agonists requires additional study to optimize efficacy while maintaining the tolerable safety profile.
- Keywords
- Adult; Antibodies, Monoclonal, Humanized; *Carcinoma, Non-Small-Cell Lung/drug therapy; Humans; Immune Checkpoint Inhibitors/adverse effects; Immunoglobulin G; *Lung Neoplasms/drug therapy; *Melanoma/drug therapy; Tumor Microenvironment; 4-1bb/cd137; Nsclc; immune checkpoint inhibitor; melanoma; utomilumab
- Department(s)
- Medical Oncology
- PubMed ID
- 35983060
- Publisher's Version
- https://doi.org/10.3389/fimmu.2022.897991
- Open Access at Publisher's Site
https://doi.org/10.3389/fimmu.2022.897991- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-11-08 06:56:18
Last Modified: 2024-11-08 06:56:45