A Phase 3, Randomized, Open-label Study to Evaluate Pembrolizumab as Neoadjuvant Therapy and in Combination with Standard of Care as Adjuvant Therapy for Stage III-IVB Resectable Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC)

This is a randomized, active-controlled, open-label study of pembrolizumab (Pembro) given prior to surgery and pembrolizumab in combination with standard of care radiotherapy (with or without cisplatin), as post-surgical therapy in treatment naïve participants with newly diagnosed Stage III/IVA, resectable, locoregionally advanced, head and neck squamous cell carcinoma (LA-HNSCC). The primary hypothesis is that pembrolizumab given before surgery and after surgery in combination with radiotherapy (with or without cisplatin) improves major pathological response and event-free survival compared to radiotherapy (with or without cisplatin) alone.

Inclusion Criteria:
• Has histologically confirmed new diagnosis of resectable, non-metastatic, squamous cell carcinoma that is either: Stage III Human Papillomavirus (HPV) positive oropharyngeal primary that is tumor size (T) 4, lymph node involvement (N) 0-2, no distant metastases (MO); Stage III or IVA oropharyngeal HPV negative; or Stage III or IVA larynx/hypopharynx/oral cavity primaries
• Is eligible for primary surgery based on investigator decision and per local practice
• Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI), based on RECIST version 1.1
• Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Has results from testing of HPV status for oropharyngeal cancer defined as p16

Exclusion Criteria:
• Has Stage T4B and/or N3 LA HNSCC and/or distant metastases
• Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer (HNC)
• Has received prior therapy with an anti-programmed cell death receptor 1(PD-1), anti-programmed cell death receptor ligand 1(PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor
• Has received prior radiotherapy treatment or systemic anti-cancer therapy including investigational agents for the HNC under study prior to study start
• 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 therapy
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study therapy
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. in situ cervical cancer or breast carcinoma) that have undergone potentially curative therapy
• Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis
• Has Grade ≥2 audiometric hearing loss
• Has Grade ≥2 neuropathy
• Has Grade 3-4 bleeding due to the underlying malignancy
• Has received major surgery or has not recovered adequately from the toxicity and/or complications from the intervention prior to study start
• Has had previous allogeneic tissue/solid organ transplant
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients, radiotherapy, cisplatin or their analogs
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
Phase III
Oral, Head and Neck
R Bryan Bell, M.D.
George Morris
  • Oncology and Hematology Care Westside
  • Providence Cancer Institute Franz Clinic
  • Providence Portland Medical Center