Carcinoma, Squamous Cell of Head and Neck HNSCCPhase 2InflammaSTOPNCT07840456
Safety and Efficacy of Ruxolitinib in Patients With HNSCC and High NLR Treated With Pembrolizumab - The Phase 2 InflammaSTOP Trial
A Phase 2 study testing Ruxolitinib and Pembrolizumab in people with Carcinoma, Squamous Cell of Head and Neck HNSCC, run by University Hospital, Basel, Switzerland at 10 sites in 2 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Squamous Cell of Head and Neck HNSCC
- What is being tested?
- Ruxolitinib and Pembrolizumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Nov 2026to Feb 2029
- Phase
- Phase 2
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed diagnosis of R/M HNSCC without local treatment options planned for treatment with pembrolizumab monotherapy (R/M cohort) or locally advanced HNSCC planned for perioperative treatment with pembrolizumab (neoadjuvant cohort)
- PD-L1 CPS≥1
- ECOG-performance score 0-2
- NLR >4 before start of pembrolizumab treatment
- Signed and dated written informed consent
Who cannot join
- Participation in another interventional study simultaneously and within the last 30 days prior to inclusion
- Concurrent malignancies other than disease under study within 5 years prior to inclusion, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
- Active, known, or suspected autoimmune disease requiring systemic treatment, a concomitant therapy with systemic immune suppression, up to 5 mg/d prednisolone equivalent is allowed
- Patients with severely reduced liver function (Child-Pugh Class C)
- Known allergy or hypersensitivity reaction to ruxolitinib
- Pregnancy and lactation
Show all 10Show fewer
- Any other serious or unstable medical condition that, in the Investigator's judgment, would compromise participant safety or interfere with study conduct; an active infection requiring systemic antimicrobial, antiviral, or antifungal therapy within 14 days before enrolment; or known HIV infection, active hepatitis B (HBsAg positive or detectable HBV DNA), or active hepatitis C (detectable HCV RNA)
- Thrombocytopenia (platelet count <100,000/microL) or neutropenia (absolute neutrophil count <1000/mcroL)
- Any condition that would require postponement of the planned curative surgical resection to accommodate the neoadjuvant ruxolitinib period (neoadjuvant cohort)
- Anticipated inability to observe the minimum treatment-free interval of at least 48 hours between the last ruxolitinib dose and surgery (neoadjuvant cohort)
Trial locations and contacts
10 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
10 sites in 2 countries
Germany5 sites
Uniklinik Köln
Cologne, North Rhine-Westphalia, 50937
Malte Suchan, Dr., 0049 (0)221 478-4754, malte.suchan@uk-koeln.de
Malte Suchan, Dr.
Universitätsmedizin Greifswald
Greifswald, Mecklenburg-Vorpommern, 17475
Markus Blaurock, Dr., 0049 (0)3834 - 86 6202, markus.blaurock@med.uni-greifswald.de
Markus Blaurock, Dr.
Katholisches Krankenhaus Hagen
Hagen, North Rhine-Westphalia, 58097
Jonas JH Parker, Prof. Dr., 0041 (0)2331 805 5490, hno@kkh-hagen.de
Jonas JH Park, Prof. Dr.
Asklepios Klinik St. Georg Hamburg
Hamburg, Schleswig-Holstein, 20099
Silke Tribius, Prof. Dr., 0049 (0)40 1818852368, s.tribius@asklepios.com
Silke Tribius, Prof. Dr.
Universitätslklinikum Würzburg
Würzburg, Bavaria, 97080
Urs Müller-Richter, Prof. Dr., 0049 (0)931 201-72720, mueller_u2@ukw.de
Urs Müller-Richter, Prof. Dr.
Switzerland5 sites
University Hospital Basel
Basel, Canton of Basel-City, 4031
Anna Brandt, PD Dr., 0041 (0)61 328 78 97, anna.brandt@usb.ch
Anna Brandt, PD Dr.
Ente Ospedaliero Cantonale
Bellinzona, Canton Ticino, 6500
Vittoria Espeli, Dr., 0041 (0)91 811 79 00, segretariatoOncologia.OIL@eoc.ch
Vittoria Espeli, Dr.
Seeland Cancer Center Biel
Biel/Bienne, Canton of Bern, 2502
Marco Siano, PD Dr., 0041 (0)32 327 08 08, seelandcancercenter@hin.ch
Marco Siano, PD Dr.
HOCH Health Ostschweiz
Sankt Gallen, Canton of St. Gallen, 9007
Markus Jörger, Prof. Dr., 0041 (0)71 494 29 22, markus.joerger@h-och.ch
Markus Jörger, Prof. Dr.
Universitätsspital Zürich
Zurich, Canton of Zurich, 8091
Panagiotis Balermpas, Prof. Dr., 0041 (0)44 255 35 67, panagiotis.balermpas@usz.ch
panagiotis.balermpas@usz.ch
About this study
Official title: Safety and Efficacy of Ruxolitinib in Patients With Head and Neck Squamous Cell Carcinoma and High Neutrophil-to-Lymphocyte Ratio Treated With Pembrolizumab - The Phase 2 InflammaSTOP Trial
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:
Read more
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.
Read the detailed description
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.
- Being tested
- Ruxolitinib, Pembrolizumab
- Keywords
- Head and Neck Squamous Cell Carcinoma, HNSCC, Recurrent and Metastatic Head and Neck Cancer, Pembrolizumab, Ruxolitinib, Janus Kinase Inhibitors, JAK Inhibition, Inflammatory Biomarkers, Immunotherapy, Neutrophil-to-lymphocyte ratio
- Medical subject headings
- Carcinoma, Squamous Cell Carcinoma of Head and Neck, Recurrence, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Also called Janus kinase inhibitors
Ruxolitinib administered orally on an intermittent schedule in combination with pembrolizumab.
PembrolizumabDrug
Also called Immune checkpoint inhibitor
Pembrolizumab administered as standard-of-care immune checkpoint inhibitor therapy.
| Study group | Role | What they receive |
|---|---|---|
| R/M cohort | Experimental | 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 Receives: Drug: Ruxolitinib; Drug: Pembrolizumab |
| Neoadjuvant Cohort | Experimental | 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. Receives: Drug: Ruxolitinib; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months after enrollment
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At screening, week 12, week 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2026
- Study startNov 2026 (estimated)
- Primary completionFeb 2029 (estimated)
- Study completionFeb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Squamous Cell of Head and Neck HNSCCStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Multicenter, non-randomized, two-cohort, phase 2 trial
- Masking
- None (open label)
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Clinical Trial Unit, University Hospital Basel, Switzerland
- Responsible party
- Sponsor
- Investigators
- Anna Brandt, PD Dr., Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07840456
- Sponsor's protocol ID
- th24Brandt; 2026-01363
- Acronym
- InflammaSTOP
- Status last verified
- Oct 2026
- First submitted
- 18 Sep 2026
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No