Definitive treatment of locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) often incorporates concurrent chemoradiotherapy. Platinum agents have been the backbone of systemic therapy in combined modality approaches. However, the addition of cisplatin to radiotherapy (RT) results in a modest survival benefit and is associated with multiple acute and late toxicities. The study of alternative approaches is warranted. Nivolumab (nivo), a fully human anti-programmed cell death-1 (PD-1) monoclonal antibody (mAb), has demonstrated a survival advantage when compared with standard treatment in patients with platinum-refractory recurrent or metastatic SCCHN. Combination of nivo with the CTLA-4 directed mAb ipilimumab (ipi) has yielded improvements in antitumor activity in melanoma and is under investigation in multiple other solid tumor types including SCCHN. Similarly, the combination of RT and immunotherapy leads to synergistic effects in the laboratory and has promise in early phase clinical trials. This clinical trial combines immunotherapy and RT to build upon these observations.
This is a single arm pilot trial that enrolls previously untreated patients with LA SCCHN who are candidates for curative intent, including stage IVA-B tumors of the oral cavity, oropharynx, hypopharynx, and larynx. HPV+ oropharyngeal tumors must be staged as T4, or N2c or N3 by AJCC 7th edition. Nivo and ipi are initiated 2 weeks prior to the beginning of RT. Nivo 3 mg/kg is administered every 2 weeks IV for a total of 17 doses and ipi 1 mg/kg is administered every 6 weeks for a total of 6 doses. RT (using IMRT) is prescribed as 2 Gy/fraction/day to a total dose of 70 Gy. The primary objective is the safety of the combination of nivo and ipi with RT with a focus on in-field toxicities (mucositis, dermatitis, edema, bleeding) with secondary endpoints of 1-year PFS, ORR, and OS. Exploratory correlative studies include tumor PD-L1 expression, tumor immune bias via the Th1/Th2 ratio, and exosome quantity and composition. The sample size is 24 patients following a two-stage design with 12 patients enrolled in the first stage and 12 more in the expansion cohort. Enrollment began in May 2017 and is ongoing.
Clinical trial identification
Legal entity responsible for the study
Thomas Jefferson University - Sidney Kimmel Cancer Center.
Bristol Myers Squibb.
J.M. Johnson: Pharmaceutical-sponsored investigator-initiated clinical trials funds: Bristol-Myers Squibb, AstraZeneca, Merck; Consultative services: Foundation Medicine. A. Luginbuhl, D. Cognetti, A. Argiris: Pharmaceutical sponsored investigator-initiated clinical trials funds: Bristol-Myers Squibb. J.M. Curry: Pharmaceutical-sponsored investigator-initiated clinical trials funds: AstraZeneca. All other authors have declared no conflicts of interest.