Faculty, Staff and Student Publications

Publication Date

2-1-2025

Journal

Journal of Immunotherapy and Precision Oncology

DOI

10.36401/JIPO-24-10

PMID

39816915

PMCID

PMC11728387

PubMedCentral® Posted Date

1-15-2025

Abstract

Introduction: Uveal melanoma remains a disease with aggressive behavior and poor prognosis despite advances in clinical management. Because monotherapy with immune checkpoint inhibitors has led to limited improvement in response rates, combination with other agents that act on the biological basis of oncogenesis has been proposed as a possible therapeutic strategy.

Methods: We designed a phase 1b trial to test the safety and tolerability of selinexor in combination with immune checkpoint inhibitors in patients with advanced uveal melanoma. Patients received selinexor 60 mg PO twice weekly with standard of care, commercially available immune checkpoint inhibitor of the investigator's choice. In one patient receiving nivolumab and ipilimumab as the immunotherapy backbone, selinexor 60 mg PO was given once weekly.

Results: We included 10 patients with uveal melanoma who received treatment with either selinexor plus pembrolizumab (n = 9) or selinexor plus nivolumab and ipilimumab (n = 1). The most common adverse events of any grade were neutropenia, thrombocytopenia, leukopenia, and anemia. Additional common nonhematological toxicities included hyponatremia, nausea, and vomiting. Dose reductions were required in six patients (60%). Among nine patients with evaluable disease, eight had stable disease as the best response. The median progression-free and overall survival were 6 months (95% CI: 4, not reached and 17 months (95% CI: 7, not reached), respectively.

Conclusion: The combination of selinexor and immunotherapy was safe and showed a side effect profile consistent with previous reports. Clinical benefit was achieved in most patients and should be validated in larger phase 2 trials. ClinicalTrials.gov ID: NCT02419495.

Published Open-Access

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