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.
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
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)
Single group
Ruxolitinib
DrugRuxolitinib administered orally on an intermittent schedule in combination with pembrolizumab.
Pembrolizumab
DrugPembrolizumab administered as standard-of-care immune checkpoint inhibitor therapy.
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.
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.
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.
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
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.
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.
≥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).
≥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).
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.
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University Hospital, Basel, Switzerland
Lead sponsor
Clinical Trial Unit, University Hospital Basel, Switzerland
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
