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Head and neck cancers

3883 - Phase I trial of cetuximab, intensity modulated radiotherapy (IMRT), and ipilimumab in previously untreated, locally advanced head and neck squamous cell carcinoma (PULA HNSCC)


08 Oct 2016


Head and neck cancers


Julie Bauman


Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435


J. Bauman1, R.L. Ferris2, D.A. Clump1, J. Ohr1, W. Gooding1, S. Kim2, B. Karlovits2, U. Duvvuri2, J.T. Johnson2, D. Petro1, D. Heron1

Author affiliations

  • 1 Upci, UPMC Hillman Cancer Center, 15213 - Pittsburgh/US
  • 2 Division Of Head And Neck Surgery Departments Of Otolaryngology, University of Pittsburgh, Eye and Ear Institute, 15213 - Pittsburgh/US


Abstract 3883


Concurrent IMRT with cetuximab (C), an EGFR-specific monoclonal antibody (mAb), provides suboptimal disease control in intermediate or high risk HNSCC. C induces cell-mediated immunity, but also immunosuppressive regulatory T cells (Treg) expressing CTLA-4, which correlate negatively with clinical outcomes. Thus, we conducted a phase I trial adding ipilimumab (ipi), an anti-CTLA-4 mAb, to standard C-IMRT.


Key eligibility included: stage III-IVb PULA HNSCC (pharynx, larynx); high risk (HPV-) or intermediate risk (HPV+ and either: ≥ 10 pack-year tobacco and ≥ N2 disease; or T4 or N3 disease). A 3 + 3 dose-escalation design was used to determine recommended phase II dose (RP2D, see Table). Dose limiting toxicity (DLT) was defined as any grade 4 adverse event (AE) except in-field radiation dermatitis or any immune-related (ir) AE requiring ≥ 2 weeks of systemic steroids.


From July 2013-May 2016, 18 pts enrolled: 5 larynx, 3 hypopharynx, 3 HPV- oropharynx, 7 HPV+ oropharynx; 14 smokers; 2 stage III, 13 stage IVa, 3 stage IVb. Two of 6 pts in cohort 1 experienced grade 3 ir-dermatologic DLT's, perforating folliculitis and autoimmune dermatitis, distinct from typical cetuximab-induced acneiform rash. No DLTs were observed in 6 pts completing treatment in cohort -1, which was expanded to N = 12. Among 16 pts who have completed treatment (2 ongoing), irAE included: grade 1, 2, and 3 dermatitis (2, 1, and 3 cases), grade 4 colitis (1; expansion cohort), and TPO auto-Ab-mediated, grade 1 hyperthyroidism (1). No hepatitis or hypophysitis was observed.


The RP2D for ipi in combination with standard C-IMRT is 1mg/kg dosed weeks 5, 8, 11, and 14. Dermatologic irAEs were unique to this regimen and dose-limiting; the spectrum of irAEs was otherwise typical for ipi.

Week of Treatment
1 2 3 4 5 6 7 8 11 14
IMRT 70-74 Gy, daily fractionation, 7 weeks X X X X X X X
Cetuximab 400 mg/m2 load then 250 mg/m2/week X X X X X X X X
Ipilimumab X X X X
Cohort -1: 1 mg/kg Cohort 1 (start): 3 mg/kg Cohort 2: 10 mg/kg

Clinical trial identification

Clinical trial information: NCT01935921.

Legal entity responsible for the study

Robert L. Ferris, MD, PhD, Julie E. Bauman, MD, MPH


National Cancer Institute grant P50 CA097190 (to Dr. Ferris)


J. Bauman: In the past 24 months, I have served on scientific advisory boards for the following pharmaceutical companies: Incyte, Merck-Serono, Merck, Kolltan. R.L. Ferris: Paid member Advisory Board (Ad-Hoc)- Merck, Celgene, Bristol Myers Squibb, AZ, Medimmune Grant/Research funding- VentiRx, Bristol Myers Squibb, AZ/Medimmune All other authors have declared no conflicts of interest.

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