A Phase 2 interventional study of Ruxolitinib and Pembrolizumab in Carcinoma, Squamous Cell of Head and Neck HNSCC, sponsored by University Hospital, Basel, Switzerland. Not yet recruiting at 10 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-20.
Sponsored by University Hospital, Basel, Switzerland · Phase 2, Interventional, and Treatment
The goal of this Phase 2 clinical trial is to learn if adding ruxolitinib to pembrolizumab may improve treatment outcomes in patients with head and neck squamous cell carcinoma (HNSCC) who have increased levels of systemic inflammation before treatment, as measured by the neutrophil-to-lymphocyte ratio (NLR). The investigational drug will be used outside of its approved indication (off-label use) based on its known pharmacologic mechanism and prior clinical experience in patients with myeloproliferative neoplasms and graft-versus-host disease.
The main questions it aims to answer are:
Is treatment with ruxolitinib in combination with pembrolizumab safe and well tolerated? Can the addition of ruxolitinib improve treatment outcomes compared with historical data? How does ruxolitinib affect the immune system and inflammation when given together with pembrolizumab? How does the combination treatment affect patients' quality of life?
Participants will:
Receive treatment with pembrolizumab and intermittent ruxolitinib. Undergo blood tests to assess immune responses and inflammation. Attend study visits for safety assessments and treatment monitoring. Complete quality-of-life questionnaires, where applicable.
The results of this study will help researchers better understand how inflammation and the body's immune system affect treatment outcomes in people with head and neck cancer. The findings may also help improve the design of future studies investigating new treatment combinations for this disease.
Head and neck squamous cell carcinoma (HNSCC) remains associated with poor outcomes in a substantial proportion of patients despite the introduction of immune checkpoint inhibitors. An elevated neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has been associated with reduced survival in patients receiving immune checkpoint inhibitor therapy and may identify a subgroup of patients at increased risk of poor treatment outcomes.
Janus kinase (JAK) inhibition represents a potential strategy to modulate cancer-associated systemic inflammation and the tumor immune microenvironment. Ruxolitinib, a JAK1/2 inhibitor, has demonstrated anti-inflammatory effects and may enhance the activity of immune checkpoint inhibition by reducing inflammatory signaling pathways that could contribute to treatment resistance.
This study uses a biomarker-driven treatment approach in patients with PD-L1-positive recurrent, metastatic, or locally advanced HNSCC who have evidence of increased systemic inflammation prior to treatment initiation. The study is designed to investigate the effects of combining pembrolizumab with intermittent ruxolitinib and to evaluate whether this approach can favorably influence systemic inflammation and immune responses while maintaining acceptable tolerability.
Patients with advanced HNSCC are frequently frail and may be unable to tolerate the toxicities associated with conventional chemotherapy-based treatment approaches. Consequently, there is a need for treatment strategies that are both effective and well tolerated in patients with reduced performance status. The present study therefore focuses on a population with an inflammatory high-risk phenotype and seeks to generate clinical and translational evidence to support future treatment development.
In addition to evaluating the clinical activity and tolerability of the combination regimen, the study will characterize treatment-associated changes in systemic inflammation and adaptive immune responses. The findings are intended to provide a better understanding of the relationship between inflammatory biomarkers, immune modulation, and clinical outcomes in HNSCC, and to inform the design of future randomized studies evaluating JAK inhibition in combination with immune checkpoint blockade.
2,018 studies on the registry are indexed under Squamous Cell Carcinoma of Head and Neck; 573 are open to participants now.
This study's planned enrollment of 66 is above the median of 48 across 1,653 interventional studies indexed under Squamous Cell Carcinoma of Head and Neck.
Browse Squamous Cell Carcinoma of Head and Neck studies →University Hospital, Basel, Switzerland is the lead sponsor of 990 studies on the registry; 189 are open to participants now.
Compared within Squamous Cell Carcinoma of Head and Neck, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Carcinoma. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with recurrent or metastatic (R/M) HNSCC receiving the immune checkpoint inhibitor pembrolizumab who are found to have an increased pretreatment neutrophil-to-lymphocyte ratio (NLR) receive additional intermittent treatment with ruxolitinib tablets twice daily during weeks 6-12 of pembrolizumab treatment. Pembrolizumab is administered according to local standard of care
Drug: Ruxolitinib · Drug: Pembrolizumab
Patients with curative locally advanced HNSCC receiving the immune checkpoint inhibitor pembrolizumab who are found to have an increased pretreatment neutrophil-to-lymphocyte ratio (NLR) receive additional intermittent treatment with ruxolitinib tablets twice daily from week 3 to week 5 of neoadjuvant pembrolizumab treatment. Pembrolizumab will be administered as per standard of care at the local site.
Drug: Ruxolitinib · Drug: Pembrolizumab
Ruxolitinib administered orally on an intermittent schedule in combination with pembrolizumab.
Also known as: Janus kinase inhibitors
Pembrolizumab administered as standard-of-care immune checkpoint inhibitor therapy.
Also known as: Immune checkpoint inhibitor
6-Month Progression-Free Survival Rate (R/M cohort only)
Progression-free survival is defined as the time from enrollment to the first documented disease progression or death from any cause, whichever occurs first. The outcome measure is the proportion of participants who are alive and progression-free 6 months after enrollment.
Time frame: 6 months after enrollment
Change in systematic inflammation (Neutrophil-to-Lymphocyte Ratio, NLR)
Percentage of participants achieving normalisation of the neutrophil-to-lymphocyte ratio (NLR) after completion of JAK-inhibition treatment. NLR is calculated as the absolute neutrophil count divided by the absolute lymphocyte count. Participants are considered to have achieved NLR normalisation if the post-treatment NLR meets the protocol-defined threshold for a normal NLR value.
Time frame: R/M cohort: at screening within 21 days before start of ruxolitinib or at week 6 (baseline) and at week 12. Neoadjuvant cohort: at screening within 21 days before start of ruxolitinib or at week 3 (baseline), at week 5 and at week 12.
Adherence to Planned JAK-Inhibition Treatment (R/M cohort only)
Proportion of participants who complete the planned JAK-inhibition treatment duration. Participants are considered adherent if they receive JAK-inhibition according to the protocol-defined treatment schedule and duration without premature discontinuation.
Time frame: From initiation of ruxolitinib treatment to Week 12 (up to 6 weeks of treatment).
Tumour response (R/M cohort only)
Best tumour response at week 12 by investigator assessment (objective response rate). Rationale: early signal of anti-tumour activity
Time frame: Week 12
Overall survival (R/M cohort only)
Overall survival is defined as the time from enrollment to death from any cause. Survival status will be assessed during follow-up and recorded every 6 months.
Time frame: From enrollment until death from any cause or until the end of study follow-up (up to approximately 5 years).
Quality of Life Assessed by EORTC QLQ-C30 (R/M cohort only).
Change in quality of life measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Scores are transformed to a 0-100 scale according to the EORTC scoring manual. Higher functional-scale scores indicate better functioning, whereas higher symptom-scale scores indicate greater symptom burden.
Time frame: At screening, week 12 and week 18
Quality of Life Assessed by EORTC QLQ-H&N43 (R/M cohort only)
Change in head and neck cancer-specific quality of life measured using the uropean Organization for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ-H\&N43) questionnaire. Scores are transformed to a 0-100 scale according to the EORTC scoring manual. Higher symptom scores indicate greater symptom burden.
Time frame: At screening, week 12, week 18
Plasma Inflammatory Biomarkers
Change in circulating inflammatory biomarkers, including plasma cytokines and other soluble factors, from before initiation of JAK-inhibition to after completion of JAK-inhibition treatment, measured using multi-analyte plasma assays.
Time frame: Baseline and after completion of JAK-inhibition treatment.
≥20% Increase in T Cell Richness or Diversity
Percentage of participants achieving a relative increase of at least 20% in peripheral blood T cell richness or diversity between initiation and completion of JAK-inhibition treatment, measured by T cell receptor next-generation sequencing (TCR-NGS).
Time frame: Before initiation of ruxolitinib treatment and after completion of ruxolitinib treatment (Week 6 and Week 12 in the R/M cohort; Week 3 and Week 5-6 in the neoadjuvant cohort).
≥20% Decrease in T Cell Clonality
Percentage of participants achieving a relative decrease of at least 20% in peripheral blood T cell clonality between initiation and completion of JAK-inhibition treatment, measured by T cell receptor next-generation sequencing (TCR-NGS).
Time frame: Before initiation of ruxolitinib treatment and after completion of ruxolitinib treatment (Week 6 and Week 12 in the R/M cohort; Week 3 and Week 5-6 in the neoadjuvant cohort).
T Cell Richness, Diversity, and Clonality
Levels of peripheral blood T cell richness, diversity, and clonality measured by T cell receptor next-generation sequencing (TCR-NGS) before initiation and after completion of JAK-inhibition treatment.
Time frame: Before initiation of ruxolitinib treatment and after completion of ruxolitinib treatment (Week 6 and Week 12 in the R/M cohort; Week 3 and Week 5-6 in the neoadjuvant cohort).
Safety and Tolerability
Number of participants experiencing adverse events and serious adverse events. Adverse events will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 6.0, including Grade 3 to 5 events.
Time frame: From initiation of ruxolitinib treatment through completion of safety follow-up (Week 6 to Week 18 in the R/M cohort; Week 3 to Week 12 in the neoadjuvant cohort)
Start is estimated for Nov 2026; primary completion for Feb 2029, 27 months later.
Of 298 non-industry phase 2 interventional studies under Squamous Cell Carcinoma of Head and Neck, half reached primary completion within 56 months of starting (the median), counting those still running; a quarter within 37 and three quarters within 85. This study's planned 27 months is below that.
Counting every sponsor, half of 366 studies reached it within 53 months; a quarter within 35 and three quarters within 82.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Ruxolitinib
Squamous Cell Carcinoma of Head and Neck →
University Hospital, Basel, Switzerland →