Faculty, Staff and Student Publications
Publication Date
2-1-2025
Journal
Cancer Medicine
Abstract
Background: Selinexor (SEL) is a nuclear exportin 1 inhibitor that blocks the transport of nuclear proteins, including tumor suppressors, to the cytoplasm. Preclinical data suggest that the combination of SEL with checkpoint blockade may result in improved response to immunotherapy.
Methods: NCT02419495 was a multiarm phase IB study of SEL in combination with other standard regimens in patients with advanced malignancies. Arm M utilized twice weekly oral SEL and intravenous nivolumab (NIVO). Arm N utilized weekly oral SEL with NIVO plus ipilimumab (IPI). The primary objective of this study was to evaluate the safety of SEL + NIVO and SEL + NIVO+IPI. Secondary objectives included determining the objective response rate (ORR) and progression-free survival (PFS).
Results: Twenty-nine patients were enrolled in the study, of which 26 (90%) had clear cell RCC (ccRCC). Most patients (72%, n = 21) had prior systemic therapies. All patients (100%) developed at least one treatment-emergent adverse event, and 93% had a treatment-related adverse event (TRAE). Grade ≥ 3 TRAE occurred in 31% of patients, including 10% with hyponatremia, 7% with neutropenia, and 7% with thromboembolic events. At a median follow-up of 12.4 months, the ORR in 27 patients evaluable for response was 19% (n = 5). An additional 17 patients (63%) had stable disease (SD) as the best response. The median PFS for the overall cohort was 14.5 months (95% CI 5.2-17.4 months; SEL + NIVO+IPI: 12.2 months, SEL + NIVO: 14.5 months). The median overall survival was 27.8 months (95% CI 15.3-32.5; SEL + NIVO+IPI: unreached, SEL + NIVO: 21.3 months).
Conclusions: SEL in combination with NIVO or NIVO+IPI had a potentially favorable safety profile and showed modest clinical activity in patients with advanced renal cell carcinoma.
Trial registration: This clinical trial was registered on clinicaltrials.gov (NCT02419495).
Keywords
Humans, Male, Female, Hydrazines, Middle Aged, Aged, Carcinoma, Renal Cell, Antineoplastic Combined Chemotherapy Protocols, Triazoles, Kidney Neoplasms, Immune Checkpoint Inhibitors, Adult, Nivolumab, Ipilimumab, Aged, 80 and over, Progression-Free Survival, immunotherapy, renal cell carcinoma, selinexor
DOI
10.1002/cam4.70280
PMID
39945382
PMCID
PMC11822648
PubMedCentral® Posted Date
2-13-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons