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DRUG CLASS:

XPO1 inhibitor

15d
Selinexor as a Therapeutic Target: Advances in Non-small Cell and Small Cell Lung Cancer Treatment Strategies. (PubMed, Recent Pat Anticancer Drug Discov)
Key findings highlight the effectiveness of selinexor in preclinical studies, particularly against KRAS-mutant NSCLC and in combination with chemotherapy for SCLC. The review concludes with a discussion of future directions and underscores the potential of selinexor to improve the treatment strategies for lung cancer.
Journal
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KRAS (KRAS proto-oncogene GTPase)
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KRAS mutation
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Xpovio (selinexor)
17d
Venetoclax and Selinexor in Treating Patients with Relapsed or Refractory High Risk Hematologic Malignancies (clinicaltrials.gov)
P1, N=78, Completed, Sanjay Mohan | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Sep 2024
Trial completion • Trial completion date
|
Venclexta (venetoclax) • Xpovio (selinexor)
18d
Enrollment open • Enrollment change
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CD4 (CD4 Molecule)
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Xpovio (selinexor) • dexamethasone • pomalidomide • Empliciti (elotuzumab)
21d
NPM1-fusion proteins promote myeloid leukemogenesis through XPO1-dependent HOX activation. (PubMed, Leukemia)
The XPO1 inhibitor selinexor suppressed HOX activation and colony formation driven by the NPM1-fusions...Thus, our study provides experimental evidence that both NPM1::MLF1 and NPM1::CCDC28A are oncogenes with functions similar to NPM1c. Inhibition of XPO1 and menin may be a promising strategy for the NPM1-rearranged AML.
Journal • IO biomarker
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NPM1 (Nucleophosmin 1)
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NPM1 expression
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Xpovio (selinexor)
24d
New P2 trial
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cytarabine • Xpovio (selinexor) • carmustine
28d
Allosteric degraders induce CRL5 ASB8 mediated degradation of XPO1. (PubMed, bioRxiv)
Selinexor/KPT-185 is an allosteric degrader. We have explained how drug-induced protein degradation is mediated by a CRL5 system through an allosteric rather than a molecular glue mechanism, expanding the modes of targeted protein degradation beyond the well-known molecular glues of CRL4.
Journal
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XPO1 (Exportin 1) • IL17RB (Interleukin 17 Receptor B)
|
Xpovio (selinexor)
1m
Enrollment closed • Enrollment change
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CD4 (CD4 Molecule)
|
Xpovio (selinexor) • dexamethasone • pomalidomide • Empliciti (elotuzumab)
2ms
Trial completion date
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XPO1 (Exportin 1)
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Xpovio (selinexor)
2ms
Selinexor, Daratumumab, Carfilzomib and Dexamethasone for the Treatment of High-Risk, Recurrent or Refractory Multiple Myeloma (clinicaltrials.gov)
P2, N=52, Active, not recruiting, Academic and Community Cancer Research United | Recruiting --> Active, not recruiting
Enrollment closed
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Chr t(4;14) • Chr t(14;16) • Chr del(1p)
|
Xpovio (selinexor) • Darzalex (daratumumab) • carfilzomib
2ms
Twice-per-weekSelinexor, 2 Days Melphalan (clinicaltrials.gov)
P3, N=126, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China
New P3 trial
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Xpovio (selinexor) • melphalan • fludarabine IV • busulfan
2ms
NCI-2015-00693: Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination with Multiple Standard Chemotherapy or Immunotherapy Agents in Patients with Advanced Malignancies (clinicaltrials.gov)
P1, N=221, Terminated, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Sep 2024; Administratively Complete
Trial completion date • Trial termination • Trial primary completion date • Combination therapy • IO biomarker • Metastases
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Lynparza (olaparib) • Yervoy (ipilimumab) • carboplatin • paclitaxel • doxorubicin hydrochloride • capecitabine • cyclophosphamide • pemetrexed • oxaliplatin • irinotecan • Halaven (eribulin mesylate) • Xpovio (selinexor) • daunorubicin • topotecan • leucovorin calcium • fluorouracil topical • Pemfexy (pemetrexed)
2ms
New P4 trial
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PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • NCAM1 (Neural cell adhesion molecule 1) • SDC1 (Syndecan 1) • CD27 (CD27 Molecule)
|
Xpovio (selinexor) • melphalan
2ms
New P2 trial
|
Jakafi (ruxolitinib) • Xpovio (selinexor) • Reblozyl (luspatercept-aamt)
2ms
STOMP: Selinexor and Backbone Treatments of Multiple Myeloma Patients (clinicaltrials.gov)
P1/2, N=300, Recruiting, Karyopharm Therapeutics Inc | Active, not recruiting --> Recruiting
Enrollment open • Combination therapy
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lenalidomide • bortezomib • Xpovio (selinexor) • Ninlaro (ixazomib) • Darzalex (daratumumab) • carfilzomib • pomalidomide • Empliciti (elotuzumab) • Blenrep (belantamab mafodotin-blmf) • mezigdomide (CC-92480)
3ms
Application and Research Progress of Selinexor in Hematologic Tumors Other Than Multiple Myeloma --Review (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
Meanwhile, the latest clinical trials have confirmed that whether it is a single agent or combined with other chemotherapy regimens, selinexor can also achieve good therapeutic effects in patients with leukemia and lymphoma. This review summarizes the results of preclinical studies and clinical trials of selinexor in treatment of non-MM hematological malignancies, aiming to explore how to choose single agent or in combination with other regimens as induction chemotherapy.
Review • Journal
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XPO1 (Exportin 1)
|
Xpovio (selinexor)
3ms
New P2 trial
|
oxaliplatin • Xpovio (selinexor)
3ms
New P2 trial
|
Xpovio (selinexor) • golidocitinib (DZD4205)
3ms
Safety and Efficacy of Selinexor in Combination With Pembrolizumab in Recurrent Advanced Melanoma (clinicaltrials.gov)
P2, N=15, Terminated, Karyopharm Therapeutics Inc | N=40 --> 15 | Trial completion date: Jan 2024 --> Sep 2023 | Active, not recruiting --> Terminated; The trial was terminated due to a lack of sufficient anti-melanoma tumor signal for the combination of selinexor + pembrolizumab.
Enrollment change • Trial completion date • Trial termination • Combination therapy • Metastases
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Keytruda (pembrolizumab) • Xpovio (selinexor)
3ms
BOSTON: Bortezomib, Selinexor, and Dexamethasone in Patients With Multiple Myeloma (clinicaltrials.gov)
P3, N=402, Completed, Karyopharm Therapeutics Inc | Active, not recruiting --> Completed
Trial completion
|
bortezomib • Xpovio (selinexor) • dexamethasone
3ms
Eltanexor and Venetoclax in Relapsed or Refractory Myelodysplastic Syndrome and Acute Myeloid Leukemia (clinicaltrials.gov)
P1, N=60, Recruiting, Vanderbilt-Ingram Cancer Center | Not yet recruiting --> Recruiting | Trial completion date: Dec 2027 --> Dec 2026 | Trial primary completion date: Dec 2026 --> Dec 2025
Enrollment open • Trial completion date • Trial primary completion date
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Venclexta (venetoclax) • eltanexor (KPT-8602)
3ms
New P1/2 trial • Combination therapy • IO biomarker
|
IFNG (Interferon, gamma) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • IL2 (Interleukin 2) • IL10 (Interleukin 10)
|
temozolomide • Xpovio (selinexor)
3ms
New P1/2 trial
|
carboplatin • ifosfamide • etoposide IV • Xpovio (selinexor) • dexamethasone
3ms
Personalized Selinexor-based Therapy for Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov)
P2, N=18, Active, not recruiting, University of Colorado, Denver | Recruiting --> Active, not recruiting
Enrollment closed
|
Xpovio (selinexor) • carfilzomib • dexamethasone • pomalidomide • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • dexamethasone injection
3ms
Development of a UPLC-MS/MS method for quantifying KPT-335 (Verdinexor) in feline plasma for a study of PK. (PubMed, Front Vet Sci)
The AUC0-∞ was 1589.82 ± 1003.75 ng·mL-1·h. The purpose of this study was to develop a rapid and simple UPLC-MS/MS method to detect KPT-335 concentration in cat plasma and to conduct preliminary pharmacokinetic studies to support the future application of KPT-335 in felines.
Journal
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XPO1 (Exportin 1)
3ms
Rare case of simultaneous occurrence of chronic neutrophil leukemia and T lymphoblastic lymphoma: case report and literature review. (PubMed, Ann Hematol)
After a regimen of ruxolitinib, VICLP (Vincristine, Idarubicin, Cyclophosphamide, Prednisone, Peg-asparaginase) regimen, high-dose cytarabine, and methotrexate regimens, the patient's bone marrow condition partially resolved. However, when the disease relapsed four months later, despite attempts with selinexor, venetoclax, and CAG(aclarubicin hydrochloride, Algocytidine, Granulocyte Stimulating Factor) chemotherapy, the leukocytes and peripheral blood primitive cells reduced, but the bone marrow did not achieve remission. This pathogenesis may be related to microenvironmental immune escape under prolonged inflammatory stimulation and gene disruption affecting protein function due to colony-stimulating factor 3 receptor gene (CSF3R) mutations. For this type of disease, early intervention may delay disease progression.
Review • Journal
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CSF3R (Colony Stimulating Factor 3 Receptor)
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Venclexta (venetoclax) • cytarabine • Jakafi (ruxolitinib) • cyclophosphamide • Xpovio (selinexor) • methotrexate • vincristine • prednisone • idarubicin hydrochloride • aclarubicin
3ms
Selinexor targeting XPO1 promotes PEG3 nuclear accumulation and suppresses cholangiocarcinoma progression. (PubMed, Cancer Chemother Pharmacol)
These findings suggest that selinexor inhibits the progression of cholangiocarcinoma by targeting XPO1 and promoting the nuclear accumulation of PEG3 protein, thereby hindering the cell cycle and inducing apoptosis.
Journal • IO biomarker
|
XPO1 (Exportin 1)
|
Xpovio (selinexor)
4ms
Enhanced Antitumor Activity by the Combination of Dasatinib and Selinexor in Chronic Myeloid Leukemia. (PubMed, Pharmaceuticals (Basel))
In conclusion, this study suggests that Dasatinib/Selinexor could be a promising therapeutic strategy for CML, providing new insights for new targeted therapies.
Journal • IO biomarker
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HMOX1 (Heme Oxygenase 1) • XPO1 (Exportin 1)
|
dasatinib • Xpovio (selinexor)
4ms
Unraveling the complexity of drug resistance mechanisms to SINE, T cell-engaging therapies and CELMoDs in multiple myeloma: a comprehensive review. (PubMed, Cancer Drug Resist)
This review summarizes current data on treatment with SINE, TCR therapy, and CELMoDs and explores their mechanism of resistance. Understanding these resistance mechanisms is critical for developing strategies to overcome treatment failure and improve therapeutic outcomes.
Review • Journal
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CRBN (Cereblon)
|
Xpovio (selinexor)
4ms
New P2 trial • Combination therapy
|
TET2 (Tet Methylcytosine Dioxygenase 2) • PTPN2 (Protein Tyrosine Phosphatase Non-Receptor Type 2) • DDX3X (DEAD-Box Helicase 3 X-Linked)
|
Rituxan (rituximab) • doxorubicin hydrochloride • cyclophosphamide • Xpovio (selinexor)
4ms
SEATTLE: Selinexor (Nexpovio®) (SVd) in Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov)
P=N/A, N=100, Recruiting, iOMEDICO AG | Trial completion date: Sep 2025 --> Sep 2026 | Trial primary completion date: Sep 2025 --> Sep 2026
Trial completion date • Trial primary completion date • Combination therapy
|
bortezomib • Xpovio (selinexor) • dexamethasone
4ms
Enrollment open
|
MGMT (6-O-methylguanine-DNA methyltransferase)
|
temozolomide • Xpovio (selinexor)
4ms
Electrophile Determines Cellular Phenotypes among XPO1-Targeting Small Molecules. (PubMed, J Med Chem)
Many structurally diverse electrophilic small molecules target exportin-1 (XPO1/CRM1) at cysteine 528, including the selective inhibitor of nuclear export (SINE) selinexor, which was FDA-approved as an anticancer agent in 2019...We observe that the electrophilic moiety of Cys528-targeting small molecules plays a decisive role in the cellular behavior observed, with subtle changes in electrophile structure being sufficient to convert XPO1-targeting probes to different pharmacological classes. This investigation represents a unique case study in which the electrophile functionality used to target a specific cysteine determines the pharmacological effect among diverse XPO1-targeting small molecules.
Journal
|
XPO1 (Exportin 1)
|
Xpovio (selinexor)
4ms
Altered RNA export by SF3B1 mutants confers sensitivity to nuclear export inhibition. (PubMed, Leukemia)
Clinical trials of XPO1 inhibitors, selinexor and eltanexor, in high-risk myelodysplastic neoplasms (MDS) revealed responders were enriched with SF3B1 mutations. These targets were tested in vivo using Sf3b1K700E conditional knock-in mice, which showed that the combination of eltanexor and venetoclax (BCL2 inhibitor) had a preferential sensitivity for SF3B1 mutant cells without excessive toxicity. In this study, we unveil the mechanisms underlying sensitization to XPO1 inhibition in SF3B1-mutant MDS and preclinically rationalize the combination of eltanexor and venetoclax for high-risk MDS.
Journal • IO biomarker
|
SF3B1 (Splicing Factor 3b Subunit 1) • BCL2L1 (BCL2-like 1) • XPO1 (Exportin 1)
|
Venclexta (venetoclax) • Xpovio (selinexor) • eltanexor (KPT-8602)
4ms
The RNA helicases DDX19A/B modulate selinexor sensitivity by regulating MCL1 mRNA nuclear export in leukemia cells. (PubMed, Leukemia)
We conclude that XPO1 and DDX19A/B coordinately regulate cellular MCL1 levels and propose that DDX19A/B could serve as biomarkers for selinexor treatment. Moreover, pharmacological targeting of DDX19 paralogs may represent a potential strategy to induce intrinsic apoptosis in leukemia cells.
Journal • IO biomarker
|
MCL1 (Myeloid cell leukemia 1) • XPO1 (Exportin 1)
|
Xpovio (selinexor)
4ms
Enrollment change • Trial withdrawal • Post-transplantation
|
clonoSEQ
|
lenalidomide • Xpovio (selinexor)
5ms
CDK4/6 inhibition augments anti-tumor efficacy of XPO1 inhibitor selinexor in natural killer/T-cell lymphoma. (PubMed, Cancer Lett)
Mechanistically, targeting CDK4/6 could enhance the anti-tumor efficacy of selinexor via the suppression of CDK4/6-pRb-E2F-c-Myc pathway in resistant cells, while selinexor alone could dramatically block this pathway in sensitive cells. Overall, our study provids a preclinical proof-of-concept for the use of selinexor alone or in combination with CDK4/6 inhibitors as a novel therapeutic strategy for patients with R/R NKTL.
Journal • IO biomarker
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • XPO1 (Exportin 1)
|
Xpovio (selinexor)
5ms
TOUCH: A Study of Evaluating the Safety and Efficacy of ATG-010 Combined With Chemotherapy Sequential With ATG-010 Monotherapy Maintenance in Peripheral T- and NK/T-cell Lymphoma (clinicaltrials.gov)
P1/2, N=56, Active, not recruiting, Antengene Corporation | Terminated --> Active, not recruiting | Trial completion date: May 2024 --> Dec 2024 | Trial primary completion date: May 2024 --> Dec 2024
Enrollment closed • Trial completion date • Trial primary completion date
|
carboplatin • gemcitabine • Tevimbra (tislelizumab-jsgr) • ifosfamide • oxaliplatin • etoposide IV • Xpovio (selinexor)
5ms
Phase 1/2 Trial of Selinexor (KPT-330) With Docetaxel for Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
P1/2, N=41, Terminated, University of Texas Southwestern Medical Center | Completed --> Terminated; Funding Sponsor no longer supporting study
Trial termination • Combination therapy • IO biomarker • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
docetaxel • Xpovio (selinexor)
5ms
Phase I Trial of the Selective Inhibitor of Nuclear Export, KPT-330, in Relapsed Childhood ALL and AML (clinicaltrials.gov)
P1, N=16, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jun 2024 --> Dec 2024
Trial completion date
|
Xpovio (selinexor)
5ms
New trial
|
Xpovio (selinexor)
5ms
Long-term follow-up of efficacy and safety of selinexor maintenance treatment in patients with TP53wt advanced or recurrent endometrial cancer: A subgroup analysis of the ENGOT-EN5/GOG-3055/SIENDO study. (PubMed, Gynecol Oncol)
In the phase 3 SIENDO study, selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who achieved a PR or CR following chemotherapy. These results are being further evaluated in an ongoing randomized phase 3 trial (NCT05611931).
Journal • Metastases
|
TP53 (Tumor protein P53)
|
Xpovio (selinexor)
5ms
Enrollment open
|
Jakafi (ruxolitinib) • Xpovio (selinexor) • Vonjo (pacritinib) • Ojjaara (momelotinib)