A Phase II/III Randomized Study of Maintenance Nivolumab versus Observation in Patients with Locally Advanced, Intermediate Risk HPV Positive OPCA

Objective:

Primary Objectives:

• Phase II: To assess the efficacy of concurrent definitive therapy followed by nivolumab compared with concurrent definitive therapy followed by observation in terms of progression-free survival (PFS).
• Phase III: To assess the efficacy of concurrent definitive therapy followed by nivolumab compared with concurrent definitive therapy followed by observation in terms of overall survival (OS).

Secondary Objectives:

• To further assess the efficacy of nivolumab compared with observation in terms of the relationship of baseline PD-L1 expression to clinical outcome.
• To evaluate the predictive value of HPV16 E6 and E7 DNA in saliva and plasma, at baseline, 12 weeks and 9 months after completion of radiation on PFS and OS in both arms of the study.
• To evaluate the tumor mutation burden by whole exome sequencing of the initial pretreatment tissue sample as well as samples obtained at the time of progression.
• To evaluate the association of 12 week post therapy FDG PET/CT with PFS and OS.
• To establish the prognostic value of SUVmax of primary tumor or neck nodal metastasis of baseline FDG PET/CT for OS (and/or PFS).
• To correlate SUVmax of primary tumor or nodal metastasis of baseline FDG PET/CT with PD-L1 expression (positive vs. negative).
• To correlate the post therapy (cisplatin + RT) FDG PET/CT with saliva or plasma levels of HPV DNA collected at the time of the standard 3 months PET/CT scan as well as 6 months later (i.e. 9 months post therapy) for both the observation and Nivolumab groups.
• To compare the PET based therapy response assessment (Hopkins criteria) to the RECIST 1.1 assessment at 12 week post chemoradiation therapy, for patients who have a PET/CT scan at 12 weeks.