KPT-330 blocked tumor growth and prolonged survival (p < 0.0002) compared to controls. These findings support investigating the use of KPT-330 and next-generation XPO1 inhibitors in CTCL.

P2, N=50, Active, not recruiting, Ida Bruun Kristensen | Recruiting --> Active, not recruiting

P1/2, N=15, Terminated, Shanghai Antengene Corporation Limited | N=59 --> 15 | Trial completion date: Mar 2024 --> Sep 2023 | Active, not recruiting --> Terminated; The study was stopped early because the sponsor decided to change the study-drug development strategy

Accrual is expected to be completed in 2024 with presentation of results in 2025. NCT05611931.

Adjuvant treatment for Glioblastoma Grade 4 with Temozolomide (TMZ) inevitably fails due to therapeutic resistance, necessitating new approaches...We assessed TMZ, Methotrexate (MTX), and Cytarabine (Ara-C) (apoptosis inducers) combined with XPO1/Bcl-2/Mcl-1-inhibitors (apoptosis rescue) in GB cell lines and primary GB stem-like cells (GSCs)...TMZ, MTX, and Ara-C combined with E, V, and A evidenced highly lethal effects when combined. As no significant cell death induction in mouse brain slices was observed, we conclude that this drug combination is effective in vitro and expected to have low side effects in vivo.

P1/2, N=97, Recruiting, Antengene Corporation | Trial primary completion date: Dec 2023 --> May 2024

P2, N=244, Recruiting, Karyopharm Therapeutics Inc | Phase classification: P2b --> P2

The most frequently used regimens were Seli-Pomalidomide-dexamethasone(dex) or Seli-Carfilzomib-dex (Seli-Kd) in the del17p group and Seli-Kd in the OHRC and standard-risk groups. Interestingly, our data suggest that Seli is a particularly effective bridging modality for patients preparing for CAR-T cell therapies in our population. Further investigation into this population is warranted, including in earlier lines of therapy, in hopes of seeing a more durable response.

P1, N=0, Withdrawn, St. Jude Children's Research Hospital | N=52 --> 0 | Not yet recruiting --> Withdrawn

Small molecules targeting XPO1 induce cytotoxicity, and selinexor was approved by the Food and Drug Administration in 2019 as a cancer chemotherapy for relapsed multiple myeloma...Additionally, we establish a class of XPO1-targeting small molecules capable of disrupting the chromatin binding of XPO1 without perturbing nuclear export or inducing cytotoxicity. This work defines a broad transcription regulatory role for XPO1 that is essential for T cell activation as well as a new class of XPO1 modulators to enable therapeutic targeting of XPO1 beyond oncology including in T cell-driven autoimmune disorders.

In conclusion, our work reveals that selinexor displays anti-leukemia efficacy against DNMT3AR882H AML via downregulating glutathione pathway. Combination of selinexor and BSO provides novel therapeutic strategy for AML treatment.

P1/2, N=300, Active, not recruiting, Karyopharm Therapeutics Inc | Phase classification: P1b/2 --> P1/2 | N=518 --> 300 | Trial completion date: Jan 2025 --> Apr 2027 | Trial primary completion date: Jan 2025 --> Apr 2027

P1/2, N=69, Recruiting, Barbara Ann Karmanos Cancer Institute | Phase classification: P1b/2 --> P1/2 | N=44 --> 69 | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=17, Active, not recruiting, University of Utah | Recruiting --> Active, not recruiting | N=56 --> 17 | Trial primary completion date: Mar 2024 --> Aug 2023

P1, N=56, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting

P2, N=320, Recruiting, Canadian Cancer Trials Group | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P1/2, N=210, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups.

P2, N=70, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting | Trial completion date: Feb 2025 --> Sep 2026 | Initiation date: Feb 2024 --> Nov 2024 | Trial primary completion date: Feb 2025 --> Sep 2026

P1/2, N=97, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P1/2, N=277, Active, not recruiting, Karyopharm Therapeutics Inc | Trial completion date: Aug 2024 --> Dec 2024

P2, N=141, Recruiting, Karyopharm Therapeutics Inc | Phase classification: P2b --> P2

Taken together, our findings indicate that Sel ameliorates BLM-induced pulmonary fibrosis by targeting GBP5 via NLRP3 inflammasome signaling. Thus, the XPO1 inhibitor - Sel might be a potential therapeutic agent for pulmonary fibrosis.

P2, N=21, Recruiting, Peking University People's Hospital | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Aug 2023 --> Jul 2024

P2, N=320, Recruiting, Canadian Cancer Trials Group | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

In lenalidomide refractory patients, a median PFS of 22.1 months was observed. 62% of the patients required dose modifications. In summary, although the primary endpoint of the study was not met, the combination of S-DVd showed encouraging clinical efficacy with a generally manageable safety profile representing a potential option for the treatment of RRMM patients.

P1/2, N=139, Recruiting, St. Jude Children's Research Hospital | Not yet recruiting --> Recruiting

P2, N=40, Recruiting, Loyola University | Not yet recruiting --> Recruiting

P1/2, N=139, Not yet recruiting, St. Jude Children's Research Hospital

Furthermore, the change in platelet counts before and after selinexor treatment was shown to be related to the plasma concentration at 3 h after administration, which provides the basis for therapeutic drug monitoring sampling time points and a method for predicting the occurrence of thrombocytopenia. In conclusion, the developed method can be used for the quantification of the plasma concentration of selinexor, and it is of great significance to conduct therapeutic drug monitoring for patients taking selinexor in order to enhance therapeutic effects and prevent the occurrence of adverse reactions.

P1, N=30, Not yet recruiting, Oncotherapeutics

P1, N=42, Recruiting, St. Jude Children's Research Hospital | Trial completion date: Jun 2024 --> Jul 2025

P1, N=78, Active, not recruiting, Sanjay Mohan | Trial primary completion date: Dec 2023 --> Mar 2024

P2; Not yet recruiting --> Recruiting

P=N/A, N=114, Active, not recruiting, University Health Network, Toronto | Recruiting --> Active, not recruiting | N=200 --> 114

P2, N=96, Recruiting, Hackensack Meridian Health | Phase classification: P2b --> P2 | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P1, N=52, Not yet recruiting, St. Jude Children's Research Hospital

The majority of pancreatic ductal adenocarcinoma (PDAC) patients experience disease progression while on treatment with gemcitabine and nanoparticle albumin-bound (nab)-paclitaxel (GemPac). Exporter protein exportin 1 (XPO1) inhibitor selinexor (Sel) with GemPac synergistically inhibited the growth of LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) mouse derived cell line and enhanced the survival of mice. Digital spatial profiling shows that Sel-GemPac causes broad perturbation of PDAC-supporting signalling in the KPC model.

P1/2, N=54, Recruiting, Sun Yat-sen University | Trial primary completion date: Mar 2024 --> Dec 2024

P1, N=16, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Oct 2023 --> Jun 2024

P2, N=82, Not yet recruiting, National Cancer Institute (NCI)

P2; Trial completion date: Oct 2026 --> Jan 2027 | Initiation date: Oct 2023 --> Jan 2024 | Trial primary completion date: Oct 2026 --> Jan 2027