Phase 1b Study of Combined Selinexor and Eribulin for the Treatment of Advanced Solid Tumors and Triple-Negative Breast Cancer

Authors

Blessie Elizabeth Nelson
Sadia Saleem
Senthil Damodaran
Neeta Somaiah
Sarina Piha-Paul
Julia Ann Moore
Bulent Yilmaz
Deby Ogbonna
Daniel D Karp
Ecaterina Dumbrava
Apostolia M Tsimberidou
David S Hong
Jordi Rodon Ahnert
Denái R Milton
Xiaofeng Zheng
Daniel J Booser
Nuhad K Ibrahim
Anthony P Conley
Priya Bhosale
Cristhiam M Rojas Hernandez
Debasish Tripathy
Aung Naing
Funda Meric-Bernstam

Publication Date

7-15-2023

Journal

Cancer

Abstract

BACKGROUND: Selinexor (KPT-330) is a potent inhibitor of exportin 1 (XPO1), in turn inhibiting tumor growth. Selinexor enhances the antitumor efficacy of eribulin in triple-negative breast cancer (TNBC) in vitro and in vivo. Given the unmet medical need in TNBC and sarcoma, the authors explored the safety and efficacy of this combination.

METHODS: The authors conducted a phase 1b trial of combined selinexor and eribulin using a 3 + 3 dose-escalation design in patients who had advanced solid tumors and in those who had TNBC in a dose-expansion cohort.

RESULTS: Patients with TNBC (N = 19), sarcoma (N = 9), and other cancers (N = 3) were enrolled in the dose-escalation cohort (N = 10) and in the dose-expansion cohort (N = 21). The median number lines of prior therapy received was four (range, from one to seven prior lines). The most common treatment-related adverse events for selinexor were nausea (77%), leukopenia (77%), anemia (68%), neutropenia (68%), and fatigue (48%). One dose-limiting toxicity occurred at the first dose level with prolonged grade 3 neutropenia. The recommended phase 2 dose was 80 mg of selinexor orally once per week and 1 mg/m

CONCLUSIONS: Selinexor and eribulin had an acceptable toxicity profile and modest overall efficacy with durable responses in select patients.

PLAIN LANGUAGE SUMMARY: Effective therapies for advanced, triple-negative breast cancer and sarcoma represent an unmet need. Exportin 1 is associated with the transport of cancer-related proteins. Preclinical studies have demonstrated tumor growth inhibition and enhanced tumor sensitivity in patients who receive selinexor combined with eribulin. In this phase 1b study, the authors evaluated the safety profile and clinical activity of the combination of selinexor, a potent oral inhibitor of exportin 1, and eribulin in patients with advanced cancers enriched for triple-negative breast cancer or sarcoma. The combination was well tolerated; most adverse events were mild or moderate, reversible, and managed with dose modifications or growth factor support. The combination of selinexor and eribulin produced an antitumor response, particularly in some patients with triple-negative breast cancer. This work lays the foundation for prospective investigations of the role of selinexor and eribulin in the treatment of triple-negative breast cancer.

Keywords

Humans, Triple Negative Breast Neoplasms, Prospective Studies, Sarcoma, Soft Tissue Neoplasms, Neutropenia, Antineoplastic Combined Chemotherapy Protocols

DOI

10.1002/cncr.34773

PMID

37016732

PMCID

PMC12036335

PubMedCentral® Posted Date

4-28-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes