Safety and Efficacy of Ruxolitinib in Patients With HNSCC and High NLR Treated With Pembrolizumab - The Phase 2 InflammaSTOP Trial

NCT07840456 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: th24Brandt; 2026-01363
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 10

Brief 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). 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.

Conditions

Carcinoma, Squamous Cell of Head and Neck HNSCC

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

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months after enrollment

Secondary Outcomes (6)

• Change in systematic inflammation (Neutrophil-to-Lymphocyte Ratio, NLR)

  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)

  From initiation of ruxolitinib treatment to Week 12 (up to 6 weeks of treatment).

• Tumour response (R/M cohort only)

  Week 12

• Overall survival (R/M cohort only)

  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).

  At screening, week 12 and week 18

Other Outcomes (5)

• Plasma Inflammatory Biomarkers

  Baseline and after completion of JAK-inhibition treatment.

• ≥20% Increase in T Cell Richness or Diversity

  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

  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).

Study Arms (2)

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

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. Pembolizumab will be administered as per standard of care at the local site.

Drug: Ruxolitinib; Drug: Pembrolizumab

Interventions

Ruxolitinib DRUG

Ruxolitinib administered orally on an intermittent schedule in combination with pembrolizumab.

Also known as: Janus kinase inhibitors

Neoadjuvant Cohort; R/M cohort

Pembrolizumab DRUG

Pembrolizumab administered as standard-of-care immune checkpoint inhibitor therapy.

Also known as: Immune checkpoint inhibitor

Neoadjuvant Cohort; R/M cohort

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Clinical Trial Unit, University Hospital Basel, Switzerland: collaborator
• University Hospital, Basel, Switzerland: lead

Study Sites (10)

Universitätslklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

Location

Universitätsmedizin Greifswald

Greifswald, Mecklenburg-Vorpommern, 17475, Germany

Location

Uniklinik Köln

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Katholisches Krankenhaus Hagen

Hagen, North Rhine-Westphalia, 58097, Germany

Location

Asklepios Klinik St. Georg Hamburg

Hamburg, Schleswig-Holstein, 20099, Germany

Location

University Hospital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

Seeland Cancer Center Biel

Biel/Bienne, Canton of Bern, 2502, Switzerland

Location

HOCH Health Ostschweiz

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

Location

Universitätsspital Zürich

Zurich, Canton of Zurich, 8091, Switzerland

Location

Ente Ospedaliero Cantonale

Bellinzona, Canton Ticino, 6500, Switzerland

Location

MeSH Terms

Conditions

Carcinoma; Squamous Cell Carcinoma of Head and Neck; Recurrence; Head and Neck Neoplasms

Interventions

ruxolitinib; Janus Kinase Inhibitors; pembrolizumab; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Carcinoma, Squamous Cell; Neoplasms by Site; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Anna Brandt, PD Dr.

  University Hospital, Basel, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Brandt, PD Dr.

CONTACT

(0)61 328 49 52; anna.brandt@usb.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, non-randomized, two-cohort, phase 2 trial

Study Record Dates

• First Submitted: September 18, 2026
• First Posted: September 25, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: September 25, 2026

Record last verified: 2026-09

Locations

DE (5); CH (5)