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 , and grade 1 hyperthyroidism . 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.