Xpovio (selinexor) / Karyopharm, Antengene, Menarini, NeoPharm, FORUS Therap, Jiangsu Hansoh Pharma - LARVOL DELTA

Momelotinib: Unique polypharmacology and novel combination strategies for myelofibrosis and beyond (AACR 2026) - "Notably, the XPO1 inhibitor selinexor emerged as a combination partner that both inhibited malignant cell growth and deepened hepcidin suppression. These discoveries highlight momelotinib's unique activity, both as a monotherapy for expanded indications and as an ideal combination partner to more effectively control anemia and halt disease progression in MF patients."

IO biomarker • Hematological Malignancies • Myelodysplastic Syndrome • Myelofibrosis • Oncology • ACVR1 • BMP6 • IRAK1 • JAK1 • XPO1

Targeting exportin 1 reduces cutaneous squamous cell carcinoma growth alone and in combination with 5-fluorouracil (AACR 2026) - "Background: Cutaneous squamous cell carcinoma (cSCC) affects approximately 1.8 million people annually in the US with an increasing number of cases. Inhibition of XPO1 was effective at killing cSCC cells in culture and in xenografts. Our genome-wide CRISPRi screen, identified 293 potential sensitizers of Selinexor, one of which was TYMS, the target of 5-FU. 5-FU-Selinexor combination were more effective than either agent alone, suggesting this combination may have potential for the treatment of nonmelanoma skin cancer."

Combination therapy • IO biomarker • B Cell Lymphoma • Basal Cell Carcinoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • CHEK1 • MLH1 • MSH2 • TYMS • XPO1

Astrocytes reprogram radiation-resistant glioblastoma to reveal new therapeutic vulnerabilities (AACR 2026) - "Additionally, radiation induced a therapeutic vulnerability in GBM cells when co-cultured with astrocytes, not present in GBM monocultures, to selinexor, afatinib, altiratinib, and crenolanib, with strongest effects at intermediate astrocyte:GBM ratios (10:90, 50:50). In conclusion, our study demonstrates that the presence of astrocytes alone significantly influences GBM response to therapy, and radiation therapy can further expose collateral sensitivities driven by astrocyte signaling. Modeling and mechanistically dissecting these microenvironmental interactions is essential for identifying new avenues for combination therapies that may improve outcomes in a cancer type where innovation is urgently needed."

Brain Cancer • Glioblastoma • Oncology • Solid Tumor

XPO1 as a therapeutic vulnerability in atypical teratoid rhabdoid tumors (AACR 2026) - "We demonstrate that XPO1 is a dependency in ATRT, and targeting XPO1 in combination with cytotoxic chemotherapy shows high translational potential."

IO biomarker • Brain Cancer • CNS Tumor • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor • ANXA5 • CASP3 • XPO1

ICA-1S and Selinexor decreases atypical teratoid rhabdoid tumor (ATRT) survival and proliferation (AACR 2026) - "These cell proliferation data suggest that ICA-1S and Selinexor have a synergistic effect on the ATRT cells. Furthermore, we plan on observing the effect the combination treatment on PKC-ι/Cdk7/Cdk2 and PKC-ι/Bad pathways both in-vitro and in-vivo."

Brain Cancer • CNS Tumor • Oncology • Rhabdoid Tumor • Sarcoma • CDK7 • PTEN • SMARCB1

A druggable genome screen identifies b-catenin transcription targets as desmoid cell vulnerabilities (AACR 2026) - "Inhibition of exportin-1 with selinexor or shRNA directed at XPO1 inhibited proliferation (by 51%, p<0.05), but failed to affect β-catenin subcellular localization as in other systems...Inhibition of MDM2 with milademetan or shRNA similarly increased p53 and p21 and reduced proliferation (by 60%, p<0.05)...BRD4 inhibition via shRNA or treatment with birabresib reduced proliferation (85%, p<0.01) but did not affect p53/p21 signaling... BRD4, MDM2 and XPO1 were identified as potential therapeutic targets in DT with gene products modulating p53/p21 or β-catenin activity. Both BRD4 and MDM2 represent direct transcriptional targets of β-catenin though negative regulation of MDM2 in the context of DT cell dependency on its protein product suggest secondary genetic events or environmental signaling may be necessary to counteract this potential tumor suppressive effect of β-catenin."

IO biomarker • Oncology • Sarcoma • Solid Tumor • BRD4 • CDKN1A • MDM2 • TERT • TGFBI • TP53 • XPO1

Combined AKT and XPO1 inhibition to target chimeric transcription factor-driven pediatric sarcoma pathogenesis (AACR 2026) - "Indeed, we showed treating EwS cells with selinexor, an FDA-approved exportin 1 (XPO1) inhibitor, increased nuclear PTEN protein levels...Nuclear export inhibition altered PTEN subcellular localization and increased PI3K activity, contributing to the synergy between AKT and XPO1 inhibition. This combination therapy displayed efficacy across multiple fusion-driven childhood sarcomas, supporting its potential as an effective combination targeted therapeutic strategy for chimeric transcription-factor driven pediatric sarcomas."

Clinical • IO biomarker • Ewing Sarcoma • Oncology • Osteosarcoma • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • ATF1 • EWSR1 • PAX3 • PTEN • WT1 • XPO1

Cancer Immunotherapy with IL-15Rα-armed Oncolytic Myxoma Virus Enhances Antitumor Immunity Against Solid Tumors (IMMUNOLOGY 2026) - "The present study evaluated and compared the local and distant anti-tumor efficacy of a MYXV engineered to express the IL15-IL15Rα cytokine complex and lacks the viral anti-apoptotic Bcl2 homolog M11L gene. Immunocompetent mice bearing contralateral tumors of colon carcinoma or lung metastatic melanoma were treated intratumorally on one side with vMyx-M11KO-IL15Rα alone or in combination with Selinexor, an oral chemotherapeutic that inhibits the nuclear exporter XPO-1 and enhances MYXV replication in cancer cells. We observed a significant reduction in tumor burden of both treated and untreated sides (abscopal effect) with virus alone or in combination with Selinexor when compared to the untreated group... This therapeutic combination enhanced viral replication and cancer cell death mediated by improved immune cell activation and infiltration into the tumor bed. Our results indicate that engineered oncolytic MYXV is synergistic to chemotherapy and produces an abscopal..."

Oncolytic virus • Colon Cancer • Colorectal Cancer • Melanoma • Solid Tumor • BCL2 • CD8 • IL15 • PTPRC

Targeting the p53 pathway to treat atypical teratoid rhabdoid tumors. (PubMed, Neurooncol Pediatr) - "We previously identified MDM2 as a therapeutic vulnerability in RTs and showed that treatment with the MDM2 inhibitor idasanutlin (IDA) increased survival in mice bearing MRT xenografts...We hypothesized that combining IDA with selinexor (SEL), a CNS penetrant XPO1 inhibitor, would potentiate p53-mediated activation and increase therapeutic response in vivo...The BCL-2 family of proteins was identified as key modulators of intrinsic and acquired resistance. Combining MDM2 inhibitors and XPO1 inhibitors is a promising therapeutic strategy for treating children with ATRT."

Journal • Oncology • Pediatrics • Rhabdoid Tumor • Sarcoma • BCL2

Primary analysis of the phase 3 randomized trial of selinexor and lenalidomide versus lenalidomide alone as maintenance therapy post autologous stem cell transplant for patients with newly diagnosed multiple myeloma (ALLG MM23; SEALAND) (ASH 2025) - P3 | "Introduction:Selinexor (S) is an oral selective exportin 1 inhibitor approved in relapsed multiple myeloma (MM) incombination with bortezomib (V) and dexamethasone (d)...Patients received ondansetron 8mg immediately prior to, and 8-hours following each S dose.Additional ondansetron and low-dose olanzapine were used as required for break-through nausea andvomiting...In this randomized phase III study, the addition of low-dose S to R maintenance following ASCT did notresult in a significant PFS benefit compared to R alone in NDMM. Although a higher CR rate was observedwith SR, this came at the cost of increased toxicity, including more infections, cytopenias andgastrointestinal AEs. Quality of life, as assessed by EORTC QLQ-C30 and MY20, was comparable betweenarms."

Clinical • P3 data • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Thrombocytopenia • Transplantation • XPO1

Selinexor and Venetoclax Combination in Patients With Relapsed or Refractory Acute Myeloid Leukemia. (PubMed, Am J Hematol) - P1 | "Preclinical studies showed a synergistic antileukemia activity with combination of selective XPO1 inhibitor selinexor (SEL) and venetoclax (VEN), with potential to overcome VEN resistance by reducing the anti-apoptotic protein MCL1. In conclusion, SEL-VEN was feasible and active in a heavily pretreated AML cohort, with no new toxicity signal, but survival outcomes remained poor. The second-generation XPO1-inhibitor eltanexor, combined with VEN may further improve outcomes in VEN resistant AML in an ongoing study (NCT06399640)."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Thrombocytopenia • MCL1

Selinexor enhances the sensitivity of hepatocellular carcinoma cells to sorafenib by regulating the BAX/Bcl-2/PUMA apoptotic pathway and the XPO1/p27 cell cycle pathway. (PubMed, Front Oncol) - "The combination strategy provides a novel potential approach for improving the therapeutic efficacy of sorafenib and overcoming both intrinsic and acquired sorafenib resistance in HCC. The main limitations of this study are the lack of RT-PCR verification and further detection of downstream apoptotic effector molecules, which need to be explored in future research."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • BAX • BCL2

Selinexor Maintenance Post CAR-T Cell Therapy for Multiple Myeloma (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

The Company will be meeting with the U.S. Food and Drug Administration (FDA) to discuss the totality of the data from the SENTRY trial and its supplemental new drug application (sNDA) filing plan. (Karyopharm Press Release) - "The Company plans to share additional data from the Phase 3 SENTRY trial at an upcoming medical meeting and expects to submit a manuscript to a peer-reviewed medical journal. The Company believes that potential inclusion in relevant compendia could occur in the second half of 2026."

FDA event • P3 data • Myelofibrosis

Karyopharm's Phase 3 SENTRY Trial in Myelofibrosis Met First Co-Primary Endpoint, Demonstrating Statistically Significant Improvement in Spleen Volume Reduction (Karyopharm Press Release) - "The trial met the first co-primary endpoint, demonstrating statistically significant improvement in spleen volume reduction of 35% or more (SVR35) for patients treated with the combination of selinexor plus ruxolitinib, with rapid, deep and sustained spleen volume reduction rates seen in the combination arm. The mean change in absolute total symptom score (Abs-TSS) at week 24 relative to baseline was comparable across the two arms with similar symptom improvement relative to baseline; the difference across the two arms was not statistically significant. Importantly, the topline results suggest a promising signal in overall survival (OS) for the combination arm...The combination demonstrated a manageable safety and tolerability profile consistent with the known profile of selinexor and ruxolitinib individually. No new safety signals were observed."

P3 data: top line • Myelofibrosis

Study of Selinexor With Carfilzomib, Isatuximab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=62 | Not yet recruiting | Sponsor: Natalie Callander

New P1/2 trial • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • TP53

An immune-therapeutic salvage strategy for 'functional' high-risk (FHR) multiple myeloma (MM) incorporating iberdomide, isatuximab, and dexamethasone – the IBIS study amarc 20-01. (ASH 2025) - P2 | "Of 50 pts: 28%, 32%, 16%, 12% with 0, 1, 2 or 3 high-risk chromosomal abnormalitiesrespectively; 34% fulfilling IMS2025 high-risk criteria, 54% standard-risk and 12% in whom diagnosticCG/FISH were omitted, 83% received PI-IMID 1L (76% VRd, 3% VRd+chemotherapy, 7% VRd+Selinexor),10% bortezomib-cyclophosphamide-dexamethasone (VCD), 7% lenalidomide-dexamethasone (Rd), 24%ASCT; 10% 1REF to 1L and 90% relapsed after initial response to 1L, of these 72% had ³PR to 1L. In this second planned interim analysis, IB-IS-DEX was well-tolerated, achieved early diseasecontrol and demonstrated promising efficacy in FHR MM. Preliminary ctDNA genomic analyses highlight asubstantial burden of adverse biology, with frequent del(17p), MYC copy number gains, and high cTFamong pts with PD. Updates on survival will be presented at the conference."

CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Insomnia • Multiple Myeloma • Neutropenia • Respiratory Diseases • Septic Shock • Sleep Disorder • Squamous Cell Carcinoma

Milk exosomes delivery of KPT-330 alleviates gastrointestinal adverse reactions and provides effective anti-diffuse large B-cell lymphoma therapy. (PubMed, Colloids Surf B Biointerfaces) - "Moreover, mExo-KPT-330 maintained its intact exosomal form after being transported across the intestinal epithelial barrier. Collectively, our results suggest that mExo loaded with KPT-330 has promising anti-DLBCL effects and that oral administration is beneficial for alleviating gastrointestinal adverse reactions induced by KPT-330."

Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IL12A

LONG-TERM FOLLOW-UP OF SELINEXOR MAINTENANCE TREATMENT IN PATIENTS WITH TP53 WILD TYPE ADVANCED/RECURRENT ENDOMETRIAL CANCER: INTERMEDIATE ENDPOINTS BY MISMATCH REPAIR STATUS IN THE ENGOT-EN5/GOG-3055/SIENDO STUDY (IGCS 2025) - P3 | "As of April 2024, 50% of patients in the TP53wt subgroup discontinued selinexor and initiated subsequent therapy vs 83% in placebo. Median TFST was 31.7 months in selinexor vs 10.6 months in placebo (HR 0.41, p=0.0002). Median PFS2 and TSST were both not reached (NR) in selinexor vs 35.2 and 22.1 months, respectively, in placebo (HR 0.62, p=0.0581; HR 0.47, p= 0.0041)."

Clinical • Metastases • Mismatch repair • Endometrial Cancer • Oncology • Solid Tumor • TP53

Inhibition of the Nuclear Export Receptor XPO1 with Selinexor Enhances Radiation Response in Endometrial Cancer Cells (SGO 2026) - No abstract available

Endometrial Cancer • Oncology • Solid Tumor

MENINGOCOCCAL SEPTICEMIA FOLLOWING CAR-T THERAPY FOR MULTIPLE MYELOMA (EBMT 2026) - " A 59-year-old male who was diagnosed with multiple myeloma in 2013, underwent bortezomib, lenalidomide, and dexamethasone (VRd)induction followed by peripheral blood stem cell transplant (PBSCT) 2013 he decided not to take lenalidomide maintenance...Post PBSCT while on lenalidomide maintenance, he had progression and was treated with daratumumab and carfilzomib...He was treated with selinexor and pomalidomide and he received CART as 5th line treatment...His grade 1 CRS was treated with dexamethasone and tocilizumab... This is the first case report of meningococcal septicemia with purpura fulminans following CART therapy. Raising awareness for infectious complication and IVIG replacement in the community oncology practice as well as implementing local treatment guidelines on IVIG replacement are key take home points. Research can determine if considering meningococcal vaccine in patients with prolonged hypogammaglobulinemia prior to CART therapy."

CAR T-Cell Therapy • Acute Kidney Injury • Hematological Malignancies • Infectious Disease • Meningococcal Infections • Multiple Myeloma • Plasmacytoma • Renal Disease • Respiratory Diseases • Septic Shock

PROGNOSTIC ANALYSIS OF ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION WITH TBI/TMLI AND VENETOCLAX-BASED CONDITIONING FOR MONOMORPHIC EPITHELIOTROPIC INTESTINAL T-CELL LYMPHOMA (EBMT 2026) - "CR was induced by surgery (n=2) or a chemotherapy regimen containing decitabine, venetoclax, gemcitabine, oxaliplatin, and pegaspargase (n=1)...Conditioning regimens consisted of TBI/venetoclax/CLAG (n=4) or TMLI/venetoclax/selinexor/CLAG (n=5). All patients received GVHD prophylaxis with anti-thymocyte globulin, cyclosporine A, and short-course methotrexate... Allo-HSCT using TBI/TMLI plus venetoclax shows promising efficacy against MEITL. The TBI+GEM+venetoclax+CLAG+ATG protocol has lower toxicity and better safety. Pre-transplant remission and no bowel obstruction predict favorable outcomes."

Acute Graft versus Host Disease • Bone Marrow Transplantation • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Liver Failure • Lymphoma • Marginal Zone Lymphoma • Peripheral T-cell Lymphoma • Respiratory Diseases • T Cell Non-Hodgkin Lymphoma • Transplantation

Refining the role of selinexor in multiple myeloma: strategic use in a shifting treatment landscape. (PubMed, ESMO Open) - "Selinexor, the first-in-class, orally bioavailable selective inhibitor of exportin 1 (XPO1), has shown encouraging results in combination with other agents, and selinexor-based therapy has been approved for the treatment of relapsed/refractory MM, with selinexor-bortezomib-dexamethasone approved for patients with at least one prior line of therapy and selinexor-dexamethasone approved in the later-relapse setting. Overall, selinexor continues to represent a valuable option, especially for patients who are ineligible to receive T-cell-redirecting therapies, or difficult-to-treat patient subgroups, where alternative strategies remain limited. Meanwhile, further data on the use of selinexor-based combinations in different settings are eagerly awaited, to help clarify its role and address persistent unmet clinical needs."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Nephrology • Oncology • Renal Disease • XPO1

Simultaneous determination of selinexor， posaconazole， venetoclax， and voriconazole in human plasma using ultra-high performance liquid chromatography-tandem mass spectrometry (PubMed, Se Pu) - "Notably， significant inter-individual variability in the peak plasma concentration （Cmax） of SEL was observed within the same treatment cycle for approximately 30% of the patient cohort. This study offers evidence-based support for personalized precision therapy in this patient population， which exhibits substantial inter-individual variability and complex drug-drug interactions in clinical practice."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology

The role of KPNA3 in multiple myeloma: implications for targeting nuclear import. (PubMed, Apoptosis) - "Finally, both in vitro and in vivo experiments revealed that IVM and selinexor exhibited synergistic anti-MM activities. Overall, our study reveals the role of KPNA3 in MM and suggests that targeting its nuclear import is a promising MM treatment."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • ALDH2 • KPNA3