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A Phase I Dose Escalation Study of Selinexor Plus Nivolumab and Ipilimumab in Advanced/Metastatic Solid Malignancies | Clinical Trials | Clareo Health

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A Phase I Dose Escalation Study of Selinexor Plus Nivolumab and Ipilimumab in Advanced/Metastatic Solid Malignancies

NCT04850755•National University Hospital, Singapore

View on ClinicalTrials.gov

Summary

This is a single-centre, phase 1a (dose escalation) and 1b (dose expansion) study to evaluate the safety and tolerability of oral Selinexor in combination with nivolumab and ipilimumab in patients with advanced solid malignancies.

Detailed Description

Primary Objectives * To evaluate the safety and tolerability of selinexor in combination with nivolumab and ipilimumab * To determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and recommended phase 2 dose (RP2D) of selinexor in combination with nivolumab and ipilimumab in patients with advanced or metastatic solid tumor malignancies. Secondary Objectives * To determine Selinexor pharmacokinetics (PK) in Asian patients * To describe anti-tumor responses with the combination in patients with advanced or metastatic solid tumor malignancies. Exploratory Objectives * To assess the immunomodulatory effects of selinexor in solid tumour malignancies and circulating immune cells * To identify biomarkers of response to the combination of selinexor and nivolumab + ipilimumab. We will explore changes in PDL1 expression, T cell infiltration (including CD4 and CD8 positive cells), gene expression profiles on serial tumor biopsies pre-selinexor, post-selinexor alone, and after the combination of selinexor and ipilimumab + nivolumab where feasible.

Eligibility

Age

21 - 99 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Age ≥ 21
•2. Willing and able to provide written informed consent in accordance with local institutional guidelines.
•3. Dose Escalation Phase: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have radiological evidence of progressive disease on study entry that is deemed unlikely to benefit from further standard therapy.
•4. Dose Expansion phase: Patients with previously treated, metastatic or advanced recurrence malignancy confirmed histologically or cytologically. Patients must have evidence of progressive disease on study entry that is deemed unlikely to benefit from further standard therapy.
•5. There is no upper limit on the number of prior treatments. Hormone ablation therapy is considered an anticancer regimen. Radiation and surgery are not considered anticancer regimens.
•6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1.
•7. Adequate hepatic function within 14 days prior to C1D1:
•1. Total bilirubin \< 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 × ULN), and
•2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to \<3 × ULN.
•8. Adequate renal function within 14 days prior to C1D1 as determined by serum creatinine of ≤1.5 mg/dL OR estimated creatinine clearance of ≥ 30 mL/min, calculated using the Cockcroft and Gault formula (140 - Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female.
+11 more criteria

Exclusion Criteria

•1\. Subjects with active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B has been given for \>8 weeks and viral load is \<100 IU/ml prior to first dose of trial treatment. Subjects with untreated hepatitis C virus (HCV) are allowed. Subjects with Human Immunodeficiency Virus (HIV) who have CD4+ T-cell counts ≥ 350 cells/µL and no history of AIDS-defining opportunistic infections in the last year are allowed.
•5\. Major surgery within 2 weeks of first dose of study drug. 6. Patients who are pregnant or breast-feeding; 7. Patients with significantly diseased or obstructed gastrointestinal tract, malabsorption, uncontrolled vomiting or diarrhea or inability to swallow oral medications.
•8\. Patients with serious psychiatric or medical conditions that could interfere with treatment.
•9\. History of organ allograft 10. Patients who had previous grade 4 immune related adverse events from prior immunotherapy (including anti PD-1/PD-L1 or anti CTLA-4 antibodies).
•11\. Patients who previously received Selinexor and had grade 4 non laboratory adverse events that were considered treatment related or possibly treatment related.
•12\. Concurrent therapy with approved or investigational anticancer therapeutics; 13. Patients receiving chronic treatment with systemic steroid therapy (\>10 mg/day prednisone or equivalent) within 7 days of the first dose of study treatment, other than replacement-dose steroids in the setting of adrenal insufficiency. Topical,inhaled, nasal and ophthalmic steroids are not prohibited.
•14\. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
•1. Subjects with vitiligo or alopecia
•2. Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
•3. Any chronic skin condition that does not require systemic therapy
+3 more criteria

Locations (1)

National University Hospital, Singapore

Singapore, Singapore

Key Dates

Start Date

March 8, 2021

Primary Completion Date

March 17, 2025

Completion Date

March 17, 2025

Last Updated

September 25, 2025

Enrollment

ACTUAL participants

Conditions

Advance Solid MalignanciesMetastatic Solid Malignancies

Interventions

Selinexor in combination with nivolumab and ipilimumab

DRUG

Effects of LBM and PPIs on Pharmacokinetics and Safety of Regorafenib (BAY 73-4506) in Cancer Patients

NCT02439723

Metastatic Solid MalignanciesLocally Advanced Solid Malignancies

View study

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: September 25, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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