1057P - Phase I trial of cetuximab, intensity modulated radiotherapy (IMRT), and ipilimumab in previously untreated, locally advanced head and neck squamou...

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Cancer in Adolescents
Cancer Immunology and Immunotherapy
Head and Neck Cancers
Surgery and/or Radiotherapy of Cancer
Presenter Robert Ferris
Citation Annals of Oncology (2017) 28 (suppl_5): v372-v394. 10.1093/annonc/mdx374
Authors R.L. Ferris1, D.A. Clump2, J. Ohr3, W. Gooding3, S. Kim3, B.J. Karlovits3, U. Duvvuri3, J.T. Johnson3, D. Petro3, D.E. Heron3, J. Bauman3
  • 1Otoloaryngology, University of Pittsburgh, 15232 - Pittsburgh/US
  • 2Radiation Oncology, University of Pittsburgh, 15232 - Pittsburgh/US
  • 3Medicine, University of Pittsburgh, 15232 - Pittsburgh/US



Concurrent IMRT with cetuximab (C), an EGFR-specific antibody for PULA HNSCC is suboptimal for intermediate-risk (IR) or high risk (HR) HNSCC. CTLA-4+ Tregs dampen cellular immunity and correlate negatively with clinical outcomes. Thus, we conducted a phase I study adding ipilimumab (ipi), an anti-CTLA-4Ab to standard C-IMRT in patients (pts) with intermediate or high risk PULA HNSCC.


Key eligibility: stage III‐IVb PULA HNSCC [pharynx, larynx]; highrisk [HPV‐] or intermediate risk [HPV+ and either: ≥ 10 pack-year tobacco and ≥ N2 disease; or T4 or N3 disease]. A phase I [3 + 3] dose escalation design was used to establish a recommended phase II dose [RP2D). 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 incohort 1 experienced grade 3 dermatologic DLT’s: perforating folliculitis and autoimmune dermatitis. Cohort ‐1 was expanded to N = 12 without DLT’s. irAE included: grade 1, 2, and 3 dermatitis [2, 1, and 3 cases], grade 4 colitis [1], and grade 1 hyperthyroidism [1]. Four pts recurred, 3 of whom died. Five patients remain disease‐free for >2 years. Median follow up for disease‐free patients was 14 months [range 5 ‐ 37 months]. The probability of 2-year overall survival was 71% [95% CI: 49% ‐ 100%]. The two‐year probability of progression- free survival was 77% [95% CI: 59% ‐ 100%]. Immune biomarkers demonstrated modulation of suppressive regulatory T cell [Treg] subsets.


Ipi plus C‐IMRT is tolerable and yields acceptable survival without cytotoxic chemotherapy for IR and HR patients. The RP2D for ipi plus C‐IMRT is 1mg/kg weeks 5, 8, 11, and 14. Treg biomarkers are modulated by this type of immunotherapy.

Clinical trial identification

Clinical trial information: NCT01935921

Legal entity responsible for the study

University of Pittsburgh Cancer Institute


NIH 5P50CA097190-12 Head and Neck SPORE


R.L. Ferris: Astra-Zeneca/MedImmune: Advisory Bd, Clin trial, Research Funding Bristol-Myers Squibb: Advisory board, Clin trial, Research funding Lilly: Advisory Board Merck: Advisory Board, Clin trial Pfizer- Advisory Board VentiRx Pharmaceuticals: Research funding. D. Petro: Celgene - Advisory Board. J. Bauman: Scientific Consulting: Merck, Merck/EMD Serono, Eli Lilly, Kolltan. All other authors have declared no conflicts of interest.