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.
Resources from the same session
4900 - Molecular profiling and prognostic significance of TP53 mutations in Diffuse Large B Cell Lymphoma: identifying a high-risk subgroup
Presenter: Yuan-Kai Shi
Session: Poster Display session 3
Resources:
Abstract
3809 - Differential expression of various miRNAs in Pediatric Cytogenetically Normal Acute Myeloid Leukemia (CN-AML)
Presenter: Vikas Gaur
Session: Poster Display session 3
Resources:
Abstract
4750 - Circulating tumour cells in head and neck and non-small cell lung cancer
Presenter: Kenneth O'Byrne
Session: Poster Display session 3
Resources:
Abstract
3704 - OX40/OX40L protein expression in Non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers
Presenter: Xiaoshen Zhang
Session: Poster Display session 3
Resources:
Abstract
2235 - Effect of Serum Survivin on Survival among Non-Small Cell Lung Cancer Patients; NCI Experience
Presenter: Reham Rashed
Session: Poster Display session 3
Resources:
Abstract
2788 - Enhanced performance of prognostic estimation from TCGA RNAseq data using transfer learning.
Presenter: Helene Vanacker
Session: Poster Display session 3
Resources:
Abstract
4689 - Analysis of Circulating Tumor DNA for Early Relapse Detection in Stage III Colorectal Cancer After Adjuvant Chemotherapy
Presenter: Samuel Jacobs
Session: Poster Display session 3
Resources:
Abstract
1454 - Ascites-derived circulating microRNAs as potential diagnostic biomarkers of gastric cancer-associated malignant ascites
Presenter: Hye Sook Han
Session: Poster Display session 3
Resources:
Abstract
5574 - Results from TRIO030, a Pre-Surgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide
Presenter: Hsiao-Wang Chen
Session: Poster Display session 3
Resources:
Abstract
1787 - JMJD2A is a novel epigenetic factor of chemotherapeutic susceptibility in gastric cancer
Presenter: Yasushi Sato
Session: Poster Display session 3
Resources:
Abstract