Phase Ib study of safety and tolerability of selinexor in Asian patients with advanced solid cancers

Heong, Valerie; Goh, Mui Leng; Yong, Wei‐Peng; Soo, Ross A.; Chee, Cheng Ean; Raghav, Sunil K.; Goh, Boon Cher; Lee, S.C.; Lim, Joline Si Jing; Wong, Andrea Li Ann; Tan, David S.P.

doi:10.1093/annonc/mdy279.418

Cited by 3 publications

(3 citation statements)

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“…Moreover, the disease control rate (DCR) was greater in patients with RAS/AKT mutations (four out of 10 or 40%) than in WT patients (one out of eight or 12.5%). Finally, in a recent study assessing selinexor tolerance in Asian patients with advanced solid tumours ( n = 14), the median PFS was reported to be 42 days 232 …”

Section: Clinical Trials Of Xpo1 Inhibitorsmentioning

confidence: 99%

“…Finally, in a recent study assessing selinexor tolerance in Asian patients with advanced solid tumours (n = 14), the median PFS was reported to be 42 days. 232 To enhance our understanding of the safety and tolerability of selinexor in combination with calcium 5-fluorouracil, folinic acid and oxaliplatin (mFOLFOX6) for treating metastatic CRC, a phase I clinical trial (NCT02384850) was conducted with 10 patients. 235 Regrettably, the trial encountered a setback when dose-limiting toxicity necessitated the withdrawal of four patients.…”

Section: Crcmentioning

confidence: 99%

“…According to a study regarding the use of selinexor for the treatment of advanced solid tumours in Asia, patients with solid malignancies with PI3K/AKT/rat sarcoma (RAS) pathway mutations had a median PFS of 40 days, whereas the PFS was 32 days for the other six pancreatic cancer patients. 232 Furthermore, the study succeeded in establishing the optimal dose of selinexor for the forthcoming phase 2 study, setting the stage for subsequent efficacy validation. To further evaluate the substantial clinical efficacy of selinexor in combination with gemcitabine and nab-paclitaxel, a total of nine patients were enrolled in this study (NCT02178436).…”

Section: Pancreatic Cancermentioning

confidence: 99%

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The nuclear export protein exportin‐1 in solid malignant tumours: From biology to clinical trials

Lai,

Xu,

Dai

2024

Clinical & Translational Med

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BackgroundExportin‐1 (XPO1), a crucial protein regulating nuclear‐cytoplasmic transport, is frequently overexpressed in various cancers, driving tumor progression and drug resistance. This makes XPO1 an attractive therapeutic target. Over the past few decades, the number of available nuclear export‐selective inhibitors has been increasing. Only KPT‐330 (selinexor) has been successfully used for treating haematological malignancies, and KPT‐8602 (eltanexor) has been used for treating haematologic tumours in clinical trials. However, the use of nuclear export‐selective inhibitors for the inhibition of XPO1 expression has yet to be thoroughly investigated in clinical studies and therapeutic outcomes for solid tumours.MethodsWe collected numerous literatures to explain the efficacy of XPO1 Inhibitors in preclinical and clinical studies of a wide range of solid tumours.ResultsIn this review, we focus on the nuclear export function of XPO1 and results from clinical trials of its inhibitors in solid malignant tumours. We summarized the mechanism of action and therapeutic potential of XPO1 inhibitors, as well as adverse effects and response biomarkers.ConclusionXPO1 inhibition has emerged as a promising therapeutic strategy in the fight against cancer, offering a novel approach to targeting tumorigenic processes and overcoming drug resistance. SINE compounds have demonstrated efficacy in a wide range of solid tumours, and ongoing research is focused on optimizing their use, identifying response biomarkers, and developing effective combination therapies.Key Points Exportin‐1 (XPO1) plays a critical role in mediating nucleocytoplasmic transport and cell cycle. XPO1 dysfunction promotes tumourigenesis and drug resistance within solid tumours. The therapeutic potential and ongoing researches on XPO1 inhibitors in the treatment of solid tumours. Additional researches are essential to address safety concerns and identify biomarkers for predicting patient response to XPO1 inhibitors.

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Section: Clinical Trials Of Xpo1 Inhibitorsmentioning

confidence: 99%

Section: Crcmentioning

confidence: 99%

Section: Pancreatic Cancermentioning

confidence: 99%

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