HNSCC Clinical Trial
Official title:
Predictive Biomarkers For Response To Nivolumab In Head and Neck Squamous Cell Carcinoma
Nivolumab is FDA-approved for the treatment of patients with recurrent/metastatic Head and
Neck Squamous Cell Carcinoma (HNSCC).
HNSCC whose disease has progressed within 6 months after platinum-based chemotherapy. The
development of predictive biomarkers is needed to optimize patient benefit, minimize risk of
toxicities and guide combination strategies.
Nivolumab is FDA-approved for the treatment of patients with recurrent/metastatic Head and
Neck Squamous Carcinoma (HNSCC) whose disease has progressed within 6 months after
platinum-based chemotherapy. The development of predictive biomarkers is needed to optimize
patient benefit, minimize risk of toxicities and guide combination strategies. The greatest
focus has been on tumor-cell programmed death Ligand 1 (PD-L1) expression. Although PD-L1
positivity enriches for populations with clinical benefit, PD-L1 testing alone is
insufficient for patient selection in most malignancies. PD-L1 expression can be transient,
and intrapatient and even intratumor heterogeneity in PD- L1 tumor expression can exist.
Therefore, tumor sampling at one timepoint might not accurately reflect the state of PD1 axis
in a patient. Another important aspect is that PD-L1 immunohistochemistry alone does not take
into account factors that could impede the anti-PD1 therapy response such as whether or not
active immune cell engagement of the PD1 axis occurs in the tumor microenvironment or other
concurrent immune suppressive pathways are present.
Assessment of biomarkers at baseline may not predict benefit from immunotherapy. In a phase
II study of ipilimumab in patients with metastatic melanoma baseline tumor infiltrating
lymphocyte status was not associated with clinical activity. However, increase in tumor
infiltrating lymphocyte density in tumor biopsy samples collected after the second dose of
ipilimumab was associated with significantly greater clinical activity with ipilimumab
compared to samples without increase in lymphocyte density. For a better understanding of the
mechanisms of resistance to nivolumab in HNSCC, the investigators propose to study a cohort
of longitudinal HNSCC samples from recurrent/metastatic HNSCC patients treated with nivolumab
and identify biomarkers of response and resistance. The investigators will specifically focus
on modulation of immune phenotype (ImmR) following two cycles of nivolumab as surrogate
biomarker for response to nivolumab.
The primary endpoint will be the change in the percentage of immune cells that is caused by
nivolumab treatment. Secondary endpoint will be safety of performing a biopsy after second
nivolumab dose. Translational correlates will be tested in tumour tissue, plasma and germline
DNA.
Investigator assessment of best overall response (BOR), determined between the date of first
dose and the last tumor assessment (TA), will be image-based and scored using the RECIST 1.1.
criteria. BOR will be defined as categorical variable with 3 levels { Benefit (complete
response (CR), partial response (PR), stable disease (SD) lasting 6 months from the first
nivolumab dose), no benefit (PD, progressive disease or SD lasting less than 6 months from
the first nivolumab dose), and unknown} Longitudinal tissue biopsies will be collected from
HNSCC patients treated with nivolumab . Biopsies will be taken at baseline, 24-72 hours after
the second cycle of nivolumab and at progression.
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