Immunotherapy (Pembrolizumab) with Chemotherapy and Chemoradiation for the Treatment of Stage II-IVb Squamous Cell Cancer of the Nasal Cavity and Paranasal Sinuses, the I-NAPA Study

Inclusion Criteria

• Male/female participants who are at least 18 years of age on the day of signing informed consent with newly diagnosed, previously untreated, histologically and/or cytologically confirmed diagnosis of stage II-IVb PNS SCC will be enrolled in this study
• A male participant must agree to use a contraception during the treatment period and for at least 150 days after the last dose of study treatment and refrain from donating sperm during this period
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: * Not a woman of childbearing potential (WOCBP) OR * A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 150 days after the last dose of study treatment
• The participant provides written informed consent for the trial
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Absolute neutrophil count (ANC) >= 1500/uL (within 14 days prior to the start of study treatment)
• Platelets >= 100 000/uL (within 14 days prior to the start of study treatment)
• Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (within 14 days prior to the start of study treatment) * Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
• Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (within 14 days prior to the start of study treatment) * Creatinine clearance (CrCl) should be calculated per institutional standard
• Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (within 14 days prior to the start of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN (=< 5 x ULN for participants with liver metastases) (within 14 days prior to the start of study treatment)
• International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants (within 14 days prior to the start of study treatment)
• Activated partial thromboplastin time (aPTT) =< 1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137)
• Patients must not have received prior systemic anti-cancer therapy including investigational agents or radiation therapy for PNS SCC but could have received treatment for prior cancers if greater than 2 years * Note: if participant received major surgery, they must have recovered adequately form the toxicity and/or complications from the intervention prior to starting study treatment
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist [registered trademark]) are live attenuated vaccines and are not allowed
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (exceeding prednisone 10 mg daily or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. The use of dexamethasone up to 16 mg/day on cycle days 0-4 is permitted to prophylax for chemotherapy-related hypersensitivity, fluid retention and nausea
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years *Note: Participants with basal or squamous cell carcinoma of the skin and carcinoma in situ (e.g. breast carcinoma, cervical cancer, bladder cancer in situ) that have undergone potentially curative treatment, and prostate cancer patient in active surveillance are not excluded
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) infection
• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV) (defined as HCV ribonucleic acid [RNA] detected infection). Note: no testing for hepatitis B and hepatitis C is required unless mandated by local health authority
• Has a known history of active TB (Bacillus tuberculosis)
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
• Has had a solid organ transplant and/or allogenic bone marrow transplant