Advance Solid MalignanciesPhase 1NCT04850755
A Phase I Dose Escalation Study of Selinexor Plus Nivolumab and Ipilimumab in Advanced/Metastatic Solid Malignancies
A Phase 1 study testing Selinexor in combination with nivolumab and ipilimumab in people with Advance Solid Malignancies and Metastatic Solid Malignancies, run by National University Hospital, Singapore at 1 site in Singapore.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 99 years
- Conditions the study is for
- Advance Solid Malignancies, Metastatic Solid Malignancies
- What is being tested?
- Selinexor in combination with nivolumab and ipilimumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteSingapore
- Study dates
- 8 Mar 2021to 17 Mar 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 21Show fewer
- 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.
- Female patients of childbearing potential and fertile male patients must agree to use highly effective contraception listed below (ie, results in a low failure rate when used consistently and correctly) during the dosing period and for a period of at least 5 months after the end of treatment.
- Highly effective methods include: i. combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- 1. oral 2. intravaginal 3. transdermal ii. progestogen-only hormonal contraception associated with inhibition of ovulation:
- oral
- injectable
- implantable iii. intrauterine device iv. intrauterine hormone-releasing system v. bilateral tubal occlusion vi. vasectomized partner vii. sexual abstinence
Who cannot join
- Exclusion criteria 1. Patients with significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy; 2. Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) ≤ 3 weeks prior to cycle 1 day 1 3. Chemotherapy, or immunotherapy or any other systemic anticancer therapy ≤ 3 weeks prior to cycle 1 day 1.
- 4. Uncontrolled active infection requiring systemic antibiotics (Hepatitis B and C infection are NOT 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).
Show all 15Show fewer
- 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:
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Being tested
- Selinexor in combination with nivolumab and ipilimumab
- Keywords
- selinexor, nivolumab, ipilimumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Selinexor in combination with nivolumab and ipilimumabDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Selinexor in combination with nivolumab and ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective disease response assessment
to be made according to standard, international RECIST 1.1 criteria for solid tumors.
Measured: 3 years
progression free survival (PFS)
the time interval from the starting date of combination treatment to the date of disease progression on treatment
Measured: 3 years
duration of response (DOR)
is defined as the time from documentation of tumor response to disease progression
Measured: 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
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2021
- Study start8 Mar 2021
- Primary completion17 Mar 2025
- Study completion17 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Advance Solid MalignanciesStudies of the same condition, open and under way.
- More trials run by National University Hospital, SingaporeThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- National University Hospital, Singapore
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Shao Peng Tan, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04850755
- Sponsor's protocol ID
- CA209-7EL (BMS); IST-313 (KPT)
- Status last verified
- Sep 2025
- First submitted
- 14 Apr 2021
- Last updated
- 25 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 30610226Tan 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.
PubMed 24743138R 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.
PubMed 40502306
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study of Selinexor Plus Nivolumab and Ipilimumab in Advanced/Metastatic Solid Malignancies
- ClinicalTrials.gov ID
- NCT04850755
- Acronym / sponsor ID
- CA209-7EL (BMS); IST-313 (KPT)
- Keywords
- selinexor, nivolumab, ipilimumab
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- National University Hospital, SingaporeUniversity, hospital or other
- Study start
- 8 Mar 2021 (actual)
- Primary completion
- 17 Mar 2025 (actual)
- Study completion
- 17 Mar 2025 (actual)
- First posted
- 20 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| patients with advanced solid malignancies | Experimental | Drug: Selinexor in combination with nivolumab and ipilimumabPatients 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. |
Who may qualify
- Ages
- 21 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (15 listed)
- Exclusion criteria 1. Patients with significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy; 2. Radiation (except planned or ongoing palliative radiation to bone outside of the region of measurable disease) ≤ 3 weeks prior to cycle 1 day 1 3. Chemotherapy, or immunotherapy or any other systemic anticancer therapy ≤ 3 weeks prior to cycle 1 day 1.
- 4. Uncontrolled active infection requiring systemic antibiotics (Hepatitis B and C infection are NOT 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Selinexor in combination with nivolumab and ipilimumabPatients 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 | Drug | patients with advanced solid malignancies |
Primary outcome
Objective disease response assessment
Time frame: 3 years
to be made according to standard, international RECIST 1.1 criteria for solid tumors.
progression free survival (PFS)
Time frame: 3 years
the time interval from the starting date of combination treatment to the date of disease progression on treatment
duration of response (DOR)
Time frame: 3 years
is defined as the time from documentation of tumor response to disease progression
Duration of stable disease
Time frame: 3 years
is defined as the time from first RECIST assessment scan documenting stable disease by RECIST criteria, to disease progression
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2025.
- Results publication: PubMed 30610226Galon 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.
- Results publication: PubMed 24743138Tan 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.
- Derived from this study: PubMed 40502306R 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.
- Individual participant dataSharing planned: No
Related trials for Advance Solid Malignancies
RecruitingObservational study
Collection of Research Data and Samples From Patients Treated With Immunotherapy to Study Its Side Effects
Hematopoietic and Lymphoid Cell Neoplasm, Immune System Disorder
RecruitingPhase 1
Multi Tumor-Associated Antigen-Specific T Lymphocytes to Treat Patients With High Risk Solid Tumors
Solid Tumor
RecruitingPhase 1/2
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
Liposarcoma, Prostate Cancer
RecruitingPhase 1/2
Study of JMBI-001 in Patients With MYC-Positive Advanced Cancers
Advance Solid Tumors, Lymphoma, Non-Hodgkin
RecruitingPhase 1
A Study of KIVU-107 in Participants With Locally Advanced or Metastatic Solid Tumors
Advance Solid Tumors
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Shao Peng Tan principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Selinexor in combination with nivolumab and ipilimumab in people with Advance Solid Malignancies and Metastatic Solid Malignancies, run by National University Hospital, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective disease response assessment (time frame: 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04850755, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2025.