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

NCT04850755 | Completed Phase 1

• 1 other identifier: CA209-7EL (BMS); IST-313 (KPT)
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advance Solid Malignancies; Metastatic Solid Malignancies

Keywords

selinexor; nivolumab; ipilimumab

Outcome Measures

Primary Outcomes (4)

• Objective disease response assessment

  to be made according to standard, international RECIST 1.1 criteria for solid tumors.

  3 years

• progression free survival (PFS)

  the time interval from the starting date of combination treatment to the date of disease progression on treatment

  3 years

• duration of response (DOR)

  is defined as the time from documentation of tumor response to disease progression

  3 years

• Duration of stable disease

  is defined as the time from first RECIST assessment scan documenting stable disease by RECIST criteria, to disease progression

  3 years

Study Arms (1)

patients with advanced solid malignancies

EXPERIMENTAL

Patients will be dosed with selinexor once a week continuously in a 6 week cycle. Nivolumab will be administered on biweekly of each cycle . Ipilimumab will be dosed only on D1 of each cycle . Ipilimumab will continue for a maximum of 4 cycles. Nivolumab and selinexor will continue for up to 24 months or until discontinuation criteria is met.

Drug: Selinexor in combination with nivolumab and ipilimumab

Interventions

Selinexor in combination with nivolumab and ipilimumab DRUG

Patients will commence at dose level 1. One cycle is 42 days (6 weeks) for all three agents. At dose level 1, selinexor will be dosedorally weekly, and nivolumab at 2 weekly + ipilimumab 1mg/kg 6 weekly. Patients can have dosing interruptions or reductions of any drug independently of one another, depending on the drug causing the toxicity

patients with advanced solid malignancies

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 21
• Willing and able to provide written informed consent in accordance with local institutional guidelines.
• 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.
• 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.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1.
• Adequate hepatic function within 14 days prior to C1D1:
• 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
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to \<3 × ULN.
• 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.
• Adequate hematopoietic function within 14 days prior to C1D1. Transfusions and growth factors are allowed prior to and throughout the study.
• Total white blood cell (WBC) count ≥1500/mm3, absolute neutrophil count ≥1000/mm3
• Hemoglobin ≥9 g/dL
• Platelet count ≥125,000/mm3 in dose escalation phase, and platelet count ≥100,000/mm3 in dose expansion phase.
• Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 5 months following the last dose of study treatment.

You may not qualify if:

• \. 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.
• \. 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.
• \. Patients with serious psychiatric or medical conditions that could interfere with treatment.
• \. 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).
• \. Patients who previously received Selinexor and had grade 4 non laboratory adverse events that were considered treatment related or possibly treatment related.
• \. 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.
• \. 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:
• Subjects with vitiligo or alopecia
• Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Subjects without active disease in the last 5 years may be included but only after consultation with the medical monitor
• Subjects with celiac disease controlled by diet alone
• For other autoimmune or inflammatory conditions not specifically mentioned - to discuss on case by case basis with investigator and medical monitor 15. BSA \<1.35 m2 (BSA calculated by Dubois or Mosteller methods)

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital, Singapore

Singapore, Singapore

Location

Related Publications (3)

• Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019 Mar;18(3):197-218. doi: 10.1038/s41573-018-0007-y.

  PMID: 30610226 BACKGROUND

• Tan DS, Bedard PL, Kuruvilla J, Siu LL, Razak AR. Promising SINEs for embargoing nuclear-cytoplasmic export as an anticancer strategy. Cancer Discov. 2014 May;4(5):527-37. doi: 10.1158/2159-8290.CD-13-1005. Epub 2014 Apr 17.

  PMID: 24743138 BACKGROUND

• R Choo J, Jeraj SN, Sundar R, Yong WP, Lee M, Huang Y, Asokumaran Y, Chan GHJ, Ngoi NYL, Wong ALA, Soo RA, Chee CE, Lim JSJ, Goh BC, Lee SC, Tan DSP. NEXUS: a phase I dose escalation study of selinexor plus nivolumab and ipilimumab in Asian patients with advanced/metastatic solid malignancies. Ther Adv Med Oncol. 2025 Jun 9;17:17588359251339930. doi: 10.1177/17588359251339930. eCollection 2025.

  PMID: 40502306 DERIVED

MeSH Terms

Interventions

selinexor; Nivolumab; Ipilimumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• David Shao Peng Tan

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: For all patients, the phase I drug combination will be preceded by a 14-day run in period where selinexor alone will be administered and biopsies will be obtained both pre-and post selinexor dosing. Patients will be treated with all three drugs until disease progression (as defined by RECIST criteria) or intolerable drug toxicity.

Study Record Dates

• First Submitted: April 14, 2021
• First Posted: April 20, 2021
• Study Start: March 8, 2021
• Primary Completion: March 17, 2025
• Study Completion: March 17, 2025
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)