To determine if it is feasible to use neoadjuvant immunotherapy (or immunotherapy plus chemotherapy) to reduce treatment intensity and improve long-term quality of life while maintaining very high cure rates.
Subjects must have pathologically confirmed HPV-positive head and neck squamous cell carcinoma of the oropharynx. Confirmed HPV-positive disease of other subsites are uncommon but also eligible.
p16 IHC positivity is sufficient to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by Jordan and Lingen et al89).
p16 IHC positivity is to be validated using an HPV nucleic acid based secondary assay (HPV ISH, HPV PCR, HPV cfDNA) before or during the neoadjuvant phase.*
HPV DNA ISH is acceptable if positive, however a negative HPV DNA ISH should be confirmed by HPV RNA ISH or other nucleic acid based method.
Unequivocal demonstration of distant metastases (M1 disease).
Unidentifiable/unknown primary site (neither imaging nor exam nor biopsy can identify the primary). Treating physicians should agree that the primary is sufficiently identified to proceed with clinical care/treatment (e.g. in the case of imaging localization, but absence of biopsy proven pathology)
Intercurrent medical illnesses which would impair subject tolerance to therapy or limit survival. Including but not limited to ongoing or active infection, immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction, cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance. Once clinically stable, as defined by the PI, they are eligible.
Pregnant and nursing women are excluded because of the potential teratogenic effects and potential unknown effects on nursing newborns (please see above paragraph under inclusion criteria regarding WOCBP)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lead sponsor
Regeneron Pharmaceuticals
Collaborator