LBA31 - A phase Ib study of pembrolizumab (Pembro; MK-3475) in patients (Pts) with human papiilloma virus (HPV)-positive and negative head and neck cancer...

Date 28 September 2014
Event ESMO 2014
Session Head and neck cancer
Topics Immunotherapy
Head and Neck Cancers
Presenter Laura Chow
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors L.Q. Chow1, B. Burtness2, J. Weiss3, R. Berger4, J.P. Eder5, E.J. Gonzalez6, J. Pulini7, J. Johnson6, M. Dolled-Filhart8, K. Emancipator9, J.K. Lunceford10, K. Pathiraja11, C. Gause12, J.D. Cheng13, T. Seiwert14
  • 1Medical Oncology, University of Washington, 98109 - Seattle/US
  • 2Internal Medicine, Yale University School of Medicine and Yale Cancer Center, New Haven/US
  • 3Hematology And Oncology, UNC Lineberger Comprehensive Cancer Center, Chapel Hill/US
  • 4Oncology And Radiotherapy, Sheba Medical Center, Tel Hashomer/IL
  • 5Medical Oncology, Yale University, New Haven/US
  • 6Clinical Development Execution Organization – Oncology, Merck & Co., Inc., Rahway/US
  • 7Clinical Development Execution Organization, Merck & Co., Inc., Upper Gwynedd/US
  • 8Molecular Biomarkers And Diagnostics, Merck & Co., Inc., Rahway/US
  • 9Molecular Biomarkers And Diagnostics, Merck Research Laboratories, Rahway/US
  • 10Bards, Merck & Co., Inc., Provo/US
  • 11Bards, Merck & Co., Inc., Rahway/US
  • 12Clinical Biostatistics, Merck & Co., Inc., North Wales/US
  • 13Clinical Oncology, Merck & Co., Inc., North Wales/US
  • 14Department Of Medicine, Section Of Hematology/oncology, University of Chicago, Chicago/US



Background: The highly selective, anti-PD-1 humanized monoclonal antibody pembro has shown antitumor activity in several solid tumors, including HNC. We present updated safety, tolerability, and antitumor activity of pembro for recurrent/metastatic HNC ( NCT01848834).


During screening, PD-L1 expression in archival or newly obtained tumor samples was assessed using a prototype immunohistochemistry assay; PD-L1 expression in stroma or ≥1% of tumor cells was required for study entry. Pembro 10 mg/kg was given every 2 wk until complete response, progression, unacceptable toxicity, physician decision, or consent withdrawal. Adverse events (AEs) were recorded throughout the study. Response was assessed every 8 wk. Primary end point was overall response rate (ORR) per RECIST v1.1.


Out of 104 HNC pts screened, 81 (78%) were PD-L1-positive, 61 enrolled, and 60 received ≥1 pembro dose: 23 HPV+, 37 HPV. After a median follow-up of 10.2 mo, 15 pts (25%) remain on pembro. ORR (confirmed + unconfirmed) per RECIST v1.1 by investigator review was 20%, and response duration ranged from 8+ to 41+ weeks (median not reached). 9 of 11 responders had a smaller target lesion burden (ie, sum below the median) at baseline. ORR was similar in HPV+ and HPV pts, whereas PFS and OS were longer in HPV+ pts (Table). PD-L1 expression was positively correlated with ORR (P = 0.018) and PFS (P = 0.024). ORR was 50% in the 12 pts with high PD-L1 expression. Drug-related AEs of any grade occurred in 58% of pts (grade ≥3 in 17%). The most common drug-related AEs were fatigue (18%), pruritus (10%), and nausea (8%). There were no drug-related deaths.


Pembro is safe and tolerable and shows antitumor activity in both HPV+ and HPV advanced HNC. These findings support further development of pembro in advanced HNC.

OverallN = 61* HPV+n = 23* HPVn = 38*
ORR, n (%) 11 (20) 4 (20) 7 (19)
Median PFS (95% CI), wk 9.3 (8.0-20.1) 17.2 (8.0-41.7) 8.1 (7.9-15.6)
Median OS (95% CI), mo 12.6 (8.2-12.6) NR (9.6-NR) 9.5 (3.9-12.6)

*ORR and PFS were evaluated in the 56 pts (20 HPV+, 36 HPV) who received ≥1 pembro dose and had measurable disease per RECIST v1.1 by investigator review.


L.Q. Chow: Advisory Board Member for Bristol Myers Squibb, Novartis, Celgene; Research funding from Bristol Myers Squibb, Novartis, AstraZeneca/Medimmune, Genentech/Roche, VentiRx, Pfizer, Lily/Imclone; B. Burtness: Advisory board membership for VentiRx and Novartis; Research funding from Merck, Genentech, Boehringer Ingelheim, and Pfizer; E.J. Gonzalez, J.K. Lunceford, C. Gause and J.D. Cheng: Employee of and stock ownership in Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc.; J. Pulini, J. Johnson, M. Dolled-Filhart, K. Emancipator and K. Pathiraja: Employee of Merck Sharp & Dohme, a subsidiary of Merck & Co, Inc.; T. Seiwert: Advisory board membership for Novartis and Onyx/Bayer; Research funding from Boehringer Ingelheim and Genentech; Honoraria from Merck. All other authors have declared no conflicts of interest.