11TiP - Phase 3 trial of pembrolizumab as a first-line treatment in subjects with recurrent/metastatic head and neck squamous cell carcinoma: KEYNOTE-048

Date 20 November 2015
Event ESMO Symposium on Immuno-Oncology 2015
Session Welcome reception and general Poster viewing
Topics Cancer Immunology and Immunotherapy
Head and Neck Cancers
Presenter Arkadiy Klochikhin
Citation Annals of Oncology (2015) 26 (suppl_8): 5-14. 10.1093/annonc/mdv514
Authors A. Klochikhin1, R. Greil2, E. Cohen3, J. Vermorken4, K. Harrington5, M. Tahara6, J.Y. Ge7, J. Geib7, F. Jin7, B. Burtness8
  • 1Medical Oncology, State Medical Institution, 150000 - Yaroslavl/RU
  • 2Iiird Medical Department, Paracelsus Medical University Salzburg, Salzburg/AT
  • 3Translational Science, UC San Diego, Moores Cancer Center, San Diego/US
  • 4Medical Oncology, Antwerp University Hospital, Edegem/BE
  • 5Medical Oncology, Institute of Cancer Research, London/UK
  • 6Medical Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 7Medical Oncology, Merck & Co., Inc., Kenilworth/US
  • 8Medical Oncology, Yale University, New Haven/US



Cetuximab plus platinum and 5-fluorouracil (5-FU) is the only category 1 evidence-supported combination regimen recommended by current guidelines as first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Given the regimen's toxicities, there is unmet medical need in this area. Colocalization of T cells expressing programmed death-1 (PD-1) receptor and tumor cells expressing its ligands, PD-L1 and PD-L2, facilitates immune evasion in HNSCC. Pembrolizumab is a potent and highly selective humanized monoclonal antibody that directly blocks the interaction of PD-1 and each of its ligands; preliminary data from the KEYNOTE-012 trial suggest that durable response is demonstrated by pembrolizumab for R/M HNSCC patients.

Trial design

This is a randomized, active-controlled, open-label, phase 3 trial to determine efficacy and safety of pembrolizumab as monotherapy or in combination with chemotherapy relative to standard of care in patients with first-line R/M HNSCC. Key inclusion criteria: confirmed R/M HNSCC considered incurable by local therapies, no prior systemic therapy in the R/M setting, ECOG 0 or 1, and tumor biopsy tissue for PD-L1 biomarker analysis. Approximately 780 patients will be enrolled and randomly assigned 1:1:1 to (i) pembrolizumab, (ii) pembrolizumab + platinum + 5-FU, or (iii) cetuximab + platinum + 5-FU. Pembrolizumab, 5-FU, and cetuximab will be administered at doses of 200 mg every 3 weeks (Q3W), 1000 mg/m2/day over 4 days Q3W, and 400 mg/m2 (initial load) then 250 mg/m2 every week, respectively; platinum therapy will comprise cisplatin 100 mg/m2 Q3W or carboplatin AUC 5 mg/mL/min Q3W. Patients will be stratified according to PD-L1 expression status, ECOG PS, and HPV status. Primary end point is progression-free survival per RECIST 1.1 as assessed by central radiologist review. Secondary end points: overall survival, proportion progression free at 6 and 12 months, overall response rate, and response duration. Relative pharmacokinetics and safety/tolerability profile of pembrolizumab alone or in combination with chemotherapy will also be evaluated.

Clinical trial identification



A. Klochikhin: Corporate-sponsored research: Merck. J. Vermorken: Advisory board member: Merck Serono, Boehringer-Ingelheim, Vaccinogen, Synthon Pharmaceuticals, Innate Pharma, Pierre Fabre, Debiopharm, Glycotope. J.Y. Ge, J. Geib, F. Jin: Employee: Merck & Co., Inc. B. Burtness: Advisory board member: Merck, VentiRx, Amgen, Bayer, Boehringer-Ingelheim Corporate-sponsored research: Genentech, Koltan Pharmaceuticals, Merck Other (in addition to the company, describe the relationship): Johnson&Johnson, Expert Witness. All other authors have declared no conflicts of interest.