Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

Characterization of potential predictive biomarkers of response to nivolumab in CheckMate 141 in patients with squamous cell carcinoma of the head and neck (SCCHN) (#210)

Fernando Concha-Benavente 1 2 , Maura L Gillison 3 , George Blumenschein, Jr 4 , Kevin J Harrington 5 , Jerome Fayette 6 , A Dimitrios Colevas 7 , Lisa Licitra 8 , Stefan Kasper 9 , Caroline Even 10 , Francis Worden 11 , Nabil F Saba 12 , Robert Haddad 13 , Makoto Tahara 14 , Yasuhisa Hasegawa 15 , Chia-Jui Yen 16 , Mark Lynch 17 , Manish Monga 17 , William J Geese 17 , Everett E Vokes 18 , Robert L Ferris 1 2 , Diana Nazemian-Pour 19
  1. University of Pittsburgh Medical Center, Pittsburgh, PA, USA
  2. University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
  3. The Ohio State University, Columbus, OH, USA
  4. Department of Thoracic–Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
  5. Institute of Cancer Research–Royal Marsden National Institute for Health Research Biomedical Research Centre, London, UK
  6. Centre Leon Berard, Lyon, France
  7. Stanford Cancer Institute, Stanford, CA, USA
  8. Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milan, Italy
  9. University Hospital Essen, Essen, Germany
  10. Institut Gustave Roussy, Villejuif, France
  11. University of Michigan, Ann Arbor, MI, USA
  12. Winship Cancer Institute of Emory University, Atlanta, GA, USA
  13. Dana–Farber Cancer Institute, Boston, MA, USA
  14. National Cancer Center Hospital East, Kashiwa, Japan
  15. Aichi Cancer Center Hospital, Nagoya, Japan
  16. National Cheng Kung University Hospital, Tainan, Taiwan
  17. Bristol-Myers Squibb, Princeton, NJ, USA
  18. University of Chicago, Chicago, IL, USA
  19. Bristol-Myers Squibb, Mulgrave, VIC, Australia


Nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody, demonstrated longer median overall survival (7.5 vs 5.1 months) and improved response (13.3% vs 5.8%) versus investigator’s choice (IC) therapy in patients with recurrent SCCHN after platinum failure in CheckMate 141 (NCT02105636), a randomized, open-label, phase 3 trial. We screened peripheral blood lymphocytes (PBL) to identify biomarkers that may predict response to nivolumab.


Paired baseline (day 1) and on-treatment (day 43) PBL samples (n=36; 24 nivolumab; 12 IC) were analyzed using multicolor flow cytometry and a noncompeting anti-PD-1 antibody. Results were correlated with clinical outcome: responders (complete/partial response) and nonresponders (stable/progressive disease).


Levels of CD8+ T cells at baseline and on treatment were higher in nivolumab responders compared with nonresponders (23% vs 13%; P<0.05). PD-1+ CD8+ and PD-1+ CTLA-4+ CD8+ effector T cells (likely exhausted T cells) decreased ~2-fold following nivolumab in responders and nonresponders (P<0.05), whereas the decrease in CTLA-4+ CD8+ effector T cells following nivolumab was significant in responders only (8% vs 5%; P<0.05). PD-1+ TIM-3+ CD8+ effector cell levels decreased following nivolumab in nonresponders only (11% vs 7%; P<0.05); a similar nonsignificant reduction was observed in responders. PD-1+ Treg levels were lower in responders than nonresponders at baseline (19% vs 33%; P<0.01), and following nivolumab (12% vs 20%; P<0.001). As in T-effector cell populations, PD-1+ Tregs decreased ~1.6-fold after nivolumab in both responders and nonresponders (P<0.01). Baseline Ki67+ Treg levels were lower in nonresponders (28% vs 17%; P<0.05).


Response to nivolumab may be associated with higher levels of CD8+ T cells and CTLA-4+ CD8+ effector T cells, and lower PD-1+ CD8+ effector T cells and PD-1+ Tregs at baseline. Targeting both PD-1 and CTLA-4 axes is warranted in SCCHN to overcome suppressive signals in CD8+ effector T cells and in Treg cells expressing both checkpoint receptors.