TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma

Inclusion Criteria:

* Has local histologically confirmed new diagnosis of resectable, non-metastatic, SCC that is either: Stage III tumor HPV-positive oropharyngeal primary that is tumor size (T) 4, lymph node involvement (N) 0-2, no distant metastases (M) 0; Stage III or IVA oropharyngeal tumor HPV-negative; or Stage III or IVA larynx/hypopharynx/oral cavity primaries regardless of HPV status (per American Joint Committee on Cancer \[AJCC\] Staging, 8th edition).
* Has available archived or fresh core or excisional biopsy of a tumor lesion. Note: Fine needle aspirations may be allowed after discussion with Medical Monitor.
* Is eligible and plans for primary LA-HNSCC surgery based on investigator decision and per local practice.
* Has results from tumor HPV status by p16 immunohistochemistry (IHC) for oropharyngeal tumors. (HPV DNA analysis for HPV tumor status is acceptable if that is the local standard of care analysis.)
* Has adequate organ function at screening.
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
* Has at least one lesion that is deemed by the investigator to be easily and safely accessible for IT injection.

Exclusion Criteria:

* Active autoimmune conditions.
* Has significant cardiac disease.
* Has a known bleeding disorder that is deemed to place the participant at unacceptable risk for bleeding complications from IT injections or biopsies.
* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization.