This is a phase 2, pilot, randomized, open-label 3-arm study to assess the safety, tolerability, and efficacy of CUE-101 monotherapy, and CUE-101 in combination with pembrolizumab as neoadjuvant therapy in HLA-A\*0201-positive treatment naive participants with locally advanced HPV-16 associated head and neck squamous cell carcinoma (HNSCC).
Participants must have histologically or cytologically confirmed new diagnosis of locally advanced, non-metastatic, head and neck squamous cell carcinoma of the oropharynx (cT1-4 N0-N3 M0)
Inability to obtain a R0 resection with a minimally invasive surgical approach, such as Transoral Robotic Surgery (TORS)
Risk of significant functional deficit with a surgical treatment approach
Other anatomical (such as retropharyngeal location of the carotid artery) or tumor characteristics that in the surgeon's judgment would be a contra-indication to a minimally invasive surgical approach.
Has distant metastases or radiographically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis as assessed by local site investigator and radiology review.
A WOCBP who has a positive urine pregnancy test within 72 hours prior to first dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
Participants who received prior radiotherapy treatment or systemic anticancer therapy including any other investigational agents for the HNC under study prior to first dose of study drug.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug.