Selinexor Maintenance Therapy for Endometrial Cancer

(XPORT-EC-042 Trial)

Recruiting at 252 trial locations

Overseen By Bhavana Pothuri

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Karyopharm Therapeutics Inc

Must not be taking: Systemic steroids

Disqualifiers: Uterine sarcomas, Active infection, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 28-day cycles, up to 34 months

276 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether selinexor, a nuclear export inhibitor, can prevent endometrial cancer from returning after initial treatment. Participants will receive either selinexor or a placebo, as researchers assess the effectiveness and safety of selinexor as a maintenance therapy. Suitable candidates have endometrial cancer that has responded well to at least 12 weeks of platinum-based chemotherapy. As a Phase 3 trial, this study is the final step before potential FDA approval, allowing participants to contribute to a treatment nearing widespread availability.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have received any systemic anticancer therapy within 3 weeks before starting the trial. It's best to discuss your current medications with the trial team to get specific guidance.

Is there any evidence suggesting that selinexor is likely to be safe for humans?

Research has shown that selinexor is generally safe for patients with endometrial cancer. In earlier studies, patients with a specific type of this cancer, called TP53 wild-type, tolerated a 60 mg dose of selinexor once a week well.

A study of patients using selinexor for over a year indicated that the treatment is mostly safe, although some side effects might occur. In such trials, researchers closely monitor patient responses to understand and manage any side effects.

In summary, selinexor appears to be a safe option for many patients, with side effects that can usually be managed effectively. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for endometrial cancer?

Researchers are excited about selinexor for endometrial cancer because it offers a unique approach compared to current treatments like chemotherapy and hormonal therapies. Unlike these standard options, selinexor works by inhibiting XPO1, a protein that helps cancer cells survive and grow. This mechanism can potentially stop cancer cells from spreading, making it a promising maintenance therapy. Additionally, selinexor is taken as an oral tablet, which is more convenient than traditional intravenous treatments. This novel mechanism and ease of administration have researchers hopeful about its potential benefits for patients.

What evidence suggests that selinexor might be an effective treatment for endometrial cancer?

Research has shown that selinexor, which participants in this trial may receive, can significantly delay the progression of endometrial cancer. Specifically, patients with TP53 wild-type endometrial cancer experienced a median time of 39.5 months without cancer worsening when taking selinexor, compared to just 4.9 months with a placebo. This suggests that selinexor may help maintain the benefits of earlier treatments. Additionally, selinexor is generally well-tolerated by patients, indicating a promising safety profile. These findings offer hope that selinexor could be an effective ongoing treatment for some endometrial cancer patients. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or recurrent endometrial carcinoma that's p53 wild-type. They must have responded to platinum-based therapy and be able to start the study drug within 3-8 weeks after chemotherapy. Participants need good organ function, an ECOG status of 0-1, and a life expectancy over 12 weeks. Women who can bear children must test negative for pregnancy and agree to use contraception.

Inclusion Criteria

I can start the study drug 3-8 weeks after my last chemotherapy dose.

In the opinion of the Investigator, the participant must have a life expectancy of at least 12 weeks and be fit to receive investigational therapy

I am fully active or have some restrictions but can still care for myself.

Exclusion Criteria

I am taking higher than normal doses of steroids.

I do not have stomach or bowel problems affecting medicine absorption.

I have received palliative radiotherapy within the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive selinexor or placebo as maintenance therapy after achieving a response from platinum-based therapy

28-day cycles, up to 34 months

Weekly visits for dosing on Days 1, 8, 15, and 22 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Selinexor

Trial Overview The trial tests Selinexor as maintenance therapy against a placebo in patients who've had partial or complete response to previous treatment. It aims to see if Selinexor helps keep cancer from coming back or getting worse after initial success with chemotherapy.

How Is the Trial Designed?

Group I: Selinexor Experimental Treatment 1 Intervention

Participants will receive a fixed dose of selinexor 60 milligrams (mg) oral tablets once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive matching placebo for selinexor oral tablets QW on Days 1, 8, 15, and 22 of each 28-day cycle.

Who Is Running the Clinical Trial?

Karyopharm Therapeutics Inc

Lead Sponsor

Trials

89

Recruited

7,200+

Richard Paulson

Karyopharm Therapeutics Inc

Chief Executive Officer since 2021

MBA from the University of Toronto's Rotman School of Management

Reshma Rangwala

Karyopharm Therapeutics Inc

Chief Medical Officer since 2023

MD, PhD

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

Israeli Society of Gynecologic Oncology

Collaborator

Trials

4

Recruited

1,100+

Australia New Zealand Gynaecological Oncology Group

Collaborator

Trials

16

Recruited

5,800+

Belgian Gynaecological Oncology Group

Collaborator

Trials

15

Recruited

4,000+

Multicenter Italian Trials in Ovarian Cancer (MITO)

Collaborator

Trials

1

Recruited

120+

Grupo Español de Investigación en Cáncer de Ovario

Collaborator

Trials

21

Recruited

5,200+

Hellenic Cooperative Oncology Group (HeCOG)

Collaborator

Trials

1

Recruited

180+

Cancer Trials Ireland (CTI)

Collaborator

Mario Negri Gynecologic Oncology group (MaNGO)

Collaborator

Trials

3

Recruited

1,200+

Published Research Related to This Trial

Progesterone therapy shows overall response rates of 11% to 25% in well-differentiated endometrioid-type tumors, but its effectiveness can be limited by the down-regulation of progesterone receptors, suggesting a need for strategies to enhance receptor expression.

Chemotherapy combinations, particularly doxorubicin and cisplatin, yield response rates of 34% to 60%, with the addition of paclitaxel improving outcomes but increasing toxicity; ongoing studies are comparing this regimen to a less toxic alternative with carboplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: Hormonal therapy, chemotherapy and molecularly targeted therapies. Gadducci, A., Cosio, S., Genazzani, AR.[2007]

The SIENDO trial indicated that selinexor may offer clinical benefits for patients with advanced or recurrent endometrial cancer who have a TP53 wild-type status.

Despite advancements in personalized medicine, recurrent endometrial cancer remains a challenging condition, highlighting the ongoing need for new treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor: Changing the paradigm in patients with TP53 wild-type endometrial cancer? Gouda, MA., Thein, KZ.[2023]

In a phase III study involving 263 patients with advanced or recurrent endometrial cancer, selinexor showed a median progression-free survival (PFS) of 5.7 months compared to 3.8 months for placebo, although this difference did not reach statistical significance in the overall analysis.

A prespecified exploratory analysis indicated that patients with TP53 wild-type endometrial cancer experienced a significant improvement in PFS with selinexor, showing a median of 13.7 months compared to 3.7 months for placebo, suggesting potential efficacy in this specific subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer. Vergote, I., Pérez-Fidalgo, JA., Hamilton, EP., et al.[2023]

In a phase III trial, the XPO1 inhibitor selinexor provided a significant and lasting progression-free survival benefit for women with advanced or recurrent endometrial cancer that has a TP53 wild-type status.

This benefit was observed regardless of the microsatellite stability of the cancer, indicating that selinexor may be a broadly effective maintenance therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor Delays Wild-type TP53 Endometrial Cancer Progression. [2023]

Progestins are effective for treating low-grade, hormone receptor-positive endometrial cancer, with some patients experiencing prolonged survival, while combination chemotherapy regimens using platinum compounds, anthracyclines, and taxanes have shown over 50% response rates and improved overall survival beyond one year in advanced cases.

Recent advances in understanding endometrial cancer at the molecular level have led to the development of new targeted therapies, which are being investigated alongside traditional treatments, although concerns about chemotherapy-related toxicities remain significant, especially in patients with existing health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developments in the systemic treatment of endometrial cancer. Mountzios, G., Pectasides, D., Bournakis, E., et al.[2018]

Selinexor, an oral inhibitor of the nuclear export protein XPO1, shows promising antitumor activity in advanced endometrial cancer, particularly in patients with TP53 wild-type tumors, where it may reduce the risk of disease progression or death by approximately 60%.

The ongoing SIENDO and XPORT-EC trials aim to further evaluate the safety and efficacy of selinexor as a maintenance therapy after first-line chemotherapy, and preclinical studies suggest it may work well in combination with PARP inhibitors and immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selinexor in patients with advanced and recurrent endometrial cancer. Bogani, G., Monk, BJ., Coleman, RL., et al.[2023]

In a phase 2 trial involving 114 patients with heavily pretreated recurrent gynecological cancers, selinexor showed a disease control rate of 30%, indicating its potential effectiveness as a treatment option for ovarian and endometrial cancers.

Common side effects included thrombocytopenia and fatigue, but these were manageable and reversible, with lower-grade adverse events observed in patients receiving a once-weekly dosing schedule compared to twice-weekly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of the Exportin 1 inhibitor selinexor in patients with recurrent gynecological malignancies. Vergote, IB., Lund, B., Peen, U., et al.[2023]

Selinexor, an inhibitor of the exportin 1 (XPO1) receptor, showed significant cytotoxic activity against various solid tumors and acute lymphoblastic leukemia (ALL) xenografts in a study involving in vitro and in vivo testing, with 76% of solid tumor models and 63% of ALL models showing improved event-free survival.

The treatment resulted in objective responses in 4 out of 38 solid tumor xenografts and 25% of ALL xenografts, indicating its potential effectiveness, particularly in tumors with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacodynamic and genomic markers associated with response to the XPO1/CRM1 inhibitor selinexor (KPT-330): A report from the pediatric preclinical testing program. Attiyeh, EF., Maris, JM., Lock, R., et al.[2023]

Class 3 semaphorins (SEMA3B and SEMA3F) are significantly downregulated in endometrial cancer cells compared to normal tissues, indicating their potential role as tumor suppressors.

Treatment with progesterone and 1,25-dihydroxyvitamin D(3) can upregulate SEMA3B and SEMA3F, leading to inhibited cancer cell growth and reduced invasiveness, suggesting that restoring these proteins could be a promising therapeutic strategy for endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progesterone and 1,25-dihydroxyvitamin D₃ inhibit endometrial cancer cell growth by upregulating semaphorin 3B and semaphorin 3F. Nguyen, H., Ivanova, VS., Kavandi, L., et al.[2013]

The combination of selinexor and carboplatin/paclitaxel chemotherapy was found to be safe and well-tolerated in patients with advanced ovarian and endometrial cancers, with 12 patients achieving a partial response and 1 achieving a complete response.

Common treatment-related adverse events included thrombocytopenia (100%) and leukopenia (91%), indicating that while the treatment is effective, it does come with significant side effects that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I open-label study of selinexor with paclitaxel and carboplatin in patients with advanced ovarian or endometrial cancers. Rubinstein, MM., Grisham, RN., Cadoo, K., et al.[2023]

Citations

1. cancernetwork.com cancernetwork.com/view/selinexor-maintenance-improves-pfs-in-tp53-wild-type-endometrial-cancer

Selinexor Maintenance Improves PFS in TP53 Wild-Type ... The median PFS in patients with pMMR TP53 wild-type endometrial cancer was 39.5 months with selinexor and 4.9 months with placebo.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0090825824002348

Long-term follow-up of efficacy and safety of selinexor ... Selinexor maintenance therapy showed a promising efficacy signal and a manageable safety profile in the prespecified subgroup of patients with TP53wt EC who ...

3. onclive.com onclive.com/view/siendo-study-long-term-safety-and-efficacy-of-selinexor-maintenance-in-endometrial-cancer

SIENDO Study: Long-Term Safety and Efficacy of Selinexor ... Panelists discuss how selinexor shows remarkable efficacy in patients with mismatch repair–proficient endometrial cancer, with 40-month progression-free ...

4. investors.karyopharm.com investors.karyopharm.com/2024-06-01-Karyopharm-Presents-Updated-Exploratory-Subgroup-Analyses-from-SIENDO-Study-in-Patients-with-Advanced-or-Recurrent-TP53-Wild-Type-Endometrial-Cancer-During-2024-ASCO-Plenary-Series-Rapid-Abstract-Updates

Rapid Abstract Updates - Jun 1, 2024 In selinexor-treated patients with TP53 wild-type/pMMR and TP53 wild-type/dMMR endometrial cancer, median PFS was 39.5 months and 13.1 months ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.02906

Oral Selinexor as Maintenance Therapy After First-Line ... Among the 23 patients with recurrent EC, the disease control rate was 35% and the confirmed objective response rate was 9%. Tolerability was ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05611931

Study Details | NCT05611931 | Selinexor in Maintenance ... The purpose of this study is to evaluate the efficacy and safety of selinexor as a maintenance treatment in patients with p53 wt endometrial carcinoma (EC).

7. investors.karyopharm.com investors.karyopharm.com/2025-11-03-Karyopharm-Reports-Third-Quarter-2025-Financial-Results-and-Highlights-Recent-Company-Progress

Karyopharm Reports Third Quarter 2025 Financial Results ... In addition, preliminary blinded aggregate safety data from the first 61 patients with a median follow-up of greater than 12 months may suggest ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5594

Phase 3 dose selection for selinexor in TP53wt ... The integrated ER analysis demonstrates the potential for SEL 60 mg QW to be reasonably well-tolerated, while maintaining efficacy.