Abstract 5677
Background
Immune checkpoint inhibitor therapy is approved for the management of recurrent/metastatic SCCHN. However, only a subset of patients derive clinical benefit from these therapies. As an exploratory analysis in the context of a window-of-opportunity randomized trial of nivolumab in combination with the PDE5 inhibitor tadalafil, an agent that has been reported to shift immune bias in SCCHN patients, we probed immune signatures in peripheral blood and tumor samples. The complete clinical trial results as well as analysis of tumor tissue samples are reported separately.
Methods
Blood and fresh tumor samples were collected from 28 patients receiving either nivolumab alone (n = 12) or nivolumab and tadalafil (n = 16) for 4 weeks prior to surgery. Immune cell phenotypes were obtained from PBMC after red blood cell lysis using fluorescent-based flow cytometry. Plasma and short-term culture supernatant from pre-treatment biopsies and surgical specimens were analyzed by multiplex luminex analyses. Patients were segregated based on treatment group or radiographic response.
Results
Over the 4-week treatment period nivolumab altered levels of a broad range of immune mediators and this signature was slightly affected by tadalafil. Preliminary principal component analysis suggest predictive pre-treatment immune signatures consistent with T cell activation, type 1 immunity, and soluble forms of immune checkpoint receptors. As determined by FACS analysis those patients who exhibited a clinical radiographic response had lower CD4/CD8 T lymphocyte ratios and lower expression of PDL1 and CD163 on CD14+ circulating monocytes.
Conclusions
These results suggest that analytes associated with vigorous type 1 immune responses are associated with favorable therapeutic responses to PD1 inhibition in SCCHN, which was a primary endpoint of this trial. However, this is paralleled by increased expression of immune checkpoint molecules over the treatment period consistent with the hypothesis that PD1 inhibition leads to asynchronous activation/exhaustion of immune cells in the tumor and in the periphery.
Clinical trial identification
IND 135056 NCT 03238365.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Bristol-Myers Squibb.
Disclosure
All authors have declared no conflicts of interest.
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